Characterizing Frontal Lobe Seizure Semiology in Children.

OBJECTIVE: The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy. METHODS: Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4). RESULTS: Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002). INTERPRETATION: This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138-1148.

EEG-fMRI in the presurgical evaluation of temporal lobe epilepsy.

OBJECTIVE: Drug-resistant temporal lobe epilepsy (TLE) often requires thorough investigation to define the epileptogenic zone for surgical treatment. We used simultaneous interictal scalp EEG-fMRI to evaluate its value for predicting long-term postsurgical outcome. METHODS: 30 patients undergoing presurgical evaluation and proceeding to temporal lobe (TL) resection were studied. Interictal epileptiform discharges (IEDs) were identified on intra-MRI EEG and used to build a model of haemodynamic changes. In addition, topographic electroencephalographic correlation maps were calculated between the average IED during video-EEG and intra-MRI EEG, and used as a condition. This allowed the analysis of all data irrespective of the presence of IED on intra-MRI EEG. Mean follow-up after surgery was 46 months. International League Against Epilepsy (ILAE) outcomes 1 and 2 were considered good, and 3-6 poor, surgical outcome. Haemodynamic maps were classified according to the presence (Concordant) or absence (Discordant) of Blood Oxygen Level-Dependent (BOLD) change in the TL overlapping with the surgical resection. RESULTS: The proportion of patients with good surgical outcome was significantly higher (13/16; 81%) in the Concordant than in the Discordant group (3/14; 21%) (χ(2) test, Yates correction, p=0.003) and multivariate analysis showed that Concordant BOLD maps were independently related to good surgical outcome (p=0.007). Sensitivity and specificity of EEG-fMRI results to identify patients with good surgical outcome were 81% and 79%, respectively, and positive and negative predictive values were 81% and 79%, respectively. INTERPRETATION: The presence of significant BOLD changes in the area of resection on interictal EEG-fMRI in patients with TLE retrospectively confirmed the epileptogenic zone. Surgical resection including regions of haemodynamic changes in the TL may lead to better postoperative outcome.

Mapping preictal and ictal haemodynamic networks using video-electroencephalography and functional imaging.

Ictal patterns on scalp-electroencephalography are often visible only after propagation, therefore rendering localization of the seizure onset zone challenging. We hypothesized that mapping haemodynamic changes before and during seizures using simultaneous video-electroencephalography and functional imaging will improve the localization of the seizure onset zone. Fifty-five patients with ≥2 refractory focal seizures/day, and who had undergone long-term video-electroencephalography monitoring were included in the study. 'Preictal' (30 s immediately preceding the electrographic seizure onset) and ictal phases, 'ictal-onset'; 'ictalestablished' and 'late ictal', were defined based on the evolution of the electrographic pattern and clinical semiology. The functional imaging data were analysed using statistical parametric mapping to map ictal phase-related haemodynamic changes consistent across seizures. The resulting haemodynamic maps were overlaid on co-registered anatomical scans, and the spatial concordance with the presumed and invasively defined seizure onset zone was determined. Twenty patients had typical seizures during functional imaging. Seizures were identified on video-electroencephalography in 15 of 20, on electroencephalography alone in two and on video alone in three patients. All patients showed significant ictal-related haemodynamic changes. In the six cases that underwent invasive evaluation, the ictal-onset phase-related maps had a degree of concordance with the presumed seizure onset zone for all patients. The most statistically significant haemodynamic cluster within the presumed seizure onset zone was between 1.1 and 3.5 cm from the invasively defined seizure onset zone, which was resected in two of three patients undergoing surgery (Class I post-surgical outcome) and was not resected in one patient (Class III post-surgical outcome). In the remaining 14 cases, the ictal-onset phase-related maps had a degree of concordance with the presumed seizure onset zone in six of eight patients with structural-lesions and five of six non-lesional patients. The most statistically significant haemodynamic cluster was localizable at sub-lobar level within the presumed seizure onset zone in six patients. The degree of concordance of haemodynamic maps was significantly better (P < 0.05) for the ictal-onset phase [entirely concordant/concordant plus (13/20; 65%) + some concordance (4/20; 20%) = 17/20; 85%] than ictal-established [entirely concordant/concordant plus (5/13; 38%) + some concordance (4/13; 31%) = 9/13; 69%] and late ictal [concordant plus (1/9; 11%) + some concordance (4/9; 44%) = 5/9; 55%] phases. Ictal propagation-related haemodynamic changes were also seen in symptomatogenic areas (9/20; 45%) and the default mode network (13/20; 65%). A common pattern of preictal changes was seen in 15 patients, starting between 98 and 14 s before electrographic seizure onset, and the maps had a degree of concordance with the presumed seizure onset zone in 10 patients. In conclusion, preictal and ictal haemodynamic changes in refractory focal seizures can non-invasively localize seizure onset at sub-lobar/gyral level when ictal scalp-electroencephalography is not helpful.

With or without spikes: localization of focal epileptic activity by simultaneous electroencephalography and functional magnetic resonance imaging.

In patients with medically refractory focal epilepsy who are candidates for epilepsy surgery, concordant non-invasive neuroimaging data are useful to guide invasive electroencephalographic recordings or surgical resection. Simultaneous electroencephalography and functional magnetic resonance imaging recordings can reveal regions of haemodynamic fluctuations related to epileptic activity and help localize its generators. However, many of these studies (40-70%) remain inconclusive, principally due to the absence of interictal epileptiform discharges during simultaneous recordings, or lack of haemodynamic changes correlated to interictal epileptiform discharges. We investigated whether the presence of epilepsy-specific voltage maps on scalp electroencephalography correlated with haemodynamic changes and could help localize the epileptic focus. In 23 patients with focal epilepsy, we built epilepsy-specific electroencephalographic voltage maps using averaged interictal epileptiform discharges recorded during long-term clinical monitoring outside the scanner and computed the correlation of this map with the electroencephalographic recordings in the scanner for each time frame. The time course of this correlation coefficient was used as a regressor for functional magnetic resonance imaging analysis to map haemodynamic changes related to these epilepsy-specific maps (topography-related haemodynamic changes). The method was first validated in five patients with significant haemodynamic changes correlated to interictal epileptiform discharges on conventional analysis. We then applied the method to 18 patients who had inconclusive simultaneous electroencephalography and functional magnetic resonance imaging studies due to the absence of interictal epileptiform discharges or absence of significant correlated haemodynamic changes. The concordance of the results with subsequent intracranial electroencephalography and/or resection area in patients who were seizure free after surgery was assessed. In the validation group, haemodynamic changes correlated to voltage maps were similar to those obtained with conventional analysis in 5/5 patients. In 14/18 patients (78%) with previously inconclusive studies, scalp maps related to epileptic activity had haemodynamic correlates even when no interictal epileptiform discharges were detected during simultaneous recordings. Haemodynamic changes correlated to voltage maps were spatially concordant with intracranial electroencephalography or with the resection area. We found better concordance in patients with lateral temporal and extratemporal neocortical epilepsy compared to medial/polar temporal lobe epilepsy, probably due to the fact that electroencephalographic voltage maps specific to lateral temporal and extratemporal epileptic activity are more dissimilar to maps of physiological activity. Our approach significantly increases the yield of simultaneous electroencephalography and functional magnetic resonance imaging to localize the epileptic focus non-invasively, allowing better targeting for surgical resection or implantation of intracranial electrode arrays.

Microelectrode recordings in human epilepsy: a case for clinical translation.

With their 'all-or-none' action potential responses, single neurons (or units) are accepted as the basic computational unit of the brain. There is extensive animal literature to support the mechanistic importance of studying neuronal firing as a way to understand neuronal microcircuits and brain function. Although most studies have emphasized physiology, there is increasing recognition that studying single units provides novel insight into system-level mechanisms of disease. Microelectrode recordings are becoming more common in humans, paralleling the increasing use of intracranial electroencephalography recordings in the context of presurgical evaluation in focal epilepsy. In addition to single-unit data, microelectrode recordings also record local field potentials and high-frequency oscillations, some of which may be different to that recorded by clinical macroelectrodes. However, microelectrodes are being used almost exclusively in research contexts and there are currently no indications for incorporating microelectrode recordings into routine clinical care. In this review, we summarize the lessons learnt from 65 years of microelectrode recordings in human epilepsy patients. We cover the electrode constructs that can be utilized, principles of how to record and process microelectrode data and insights into ictal dynamics, interictal dynamics and cognition. We end with a critique on the possibilities of incorporating single-unit recordings into clinical care, with a focus on potential clinical indications, each with their specific evidence base and challenges.

Advances in EEG: home video telemetry, high frequency oscillations and electrical source imaging.

Over the last two decades, technological advances in electroencephalography (EEG) have allowed us to extend its clinical utility for the evaluation of patients with epilepsy. This article reviews three main areas in which substantial advances have been made in the diagnosis and pre-surgical planning of patients with epilepsy. Firstly, the development of small portable video-EEG systems have allowed some patients to record their attacks at home, thereby improving diagnosis, with consequent substantial healthcare and economic implications. Secondly, in specialist centres carrying out epilepsy surgery, there has been considerable interest in whether bursts of very high frequency EEG activity can help to determine the regions of the brain likely to be generating the seizures. Identification of these discharges, initially only recorded from intracranial electrodes, may thus allow better surgical planning and improve surgical outcomes. Finally we discuss the contribution of electrical source imaging in the pre-surgical evaluation of patients with focal epilepsy, and its prospects for the future.

Mapping human preictal and ictal haemodynamic networks using simultaneous intracranial EEG-fMRI.

Accurately characterising the brain networks involved in seizure activity may have important implications for our understanding of epilepsy. Intracranial EEG-fMRI can be used to capture focal epileptic events in humans with exquisite electrophysiological sensitivity and allows for identification of brain structures involved in this phenomenon over the entire brain. We investigated ictal BOLD networks using the simultaneous intracranial EEG-fMRI (icEEG-fMRI) in a 30 year-old male undergoing invasive presurgical evaluation with bilateral depth electrode implantations in amygdalae and hippocampi for refractory temporal lobe epilepsy. One spontaneous focal electrographic seizure was recorded. The aims of the data analysis were firstly to map BOLD changes related to the ictal activity identified on icEEG and secondly to compare different fMRI modelling approaches. Visual inspection of the icEEG showed an onset dominated by beta activity involving the right amygdala and hippocampus lasting 6.4 s (ictal onset phase), followed by gamma activity bilaterally lasting 14.8 s (late ictal phase). The fMRI data was analysed using SPM8 using two modelling approaches: firstly, purely based on the visually identified phases of the seizure and secondly, based on EEG spectral dynamics quantification. For the visual approach the two ictal phases were modelled as 'ON' blocks convolved with the haemodynamic response function; in addition the BOLD changes during the 30 s preceding the onset were modelled using a flexible basis set. For the quantitative fMRI modelling approach two models were evaluated: one consisting of the variations in beta and gamma bands power, thereby adding a quantitative element to the visually-derived models, and another based on principal components analysis of the entire spectrogram in attempt to reduce the bias associated with the visual appreciation of the icEEG. BOLD changes related to the visually defined ictal onset phase were revealed in the medial and lateral right temporal lobe. For the late ictal phase, the BOLD changes were remote from the SOZ and in deep brain areas (precuneus, posterior cingulate and others). The two quantitative models revealed BOLD changes involving the right hippocampus, amygdala and fusiform gyrus and in remote deep brain structures and the default mode network-related areas. In conclusion, icEEG-fMRI allowed us to reveal BOLD changes within and beyond the SOZ linked to very localised ictal fluctuations in beta and gamma activity measured in the amygdala and hippocampus. Furthermore, the BOLD changes within the SOZ structures were better captured by the quantitative models, highlighting the interest in considering seizure-related EEG fluctuations across the entire spectrum.

Techniques and applications of EMG: measuring motor units from structure to function.

Needle electromyography (EMG) is an established method of evaluating motor unit and muscle fibre function and pathology in clinical practice, while the development of advanced techniques including single-fibre EMG and combined recordings with other modalities have become increasingly useful in research. The development of quantitative EMG in particular had led to greater reproducibility and inter-rater reliability. This review provides an overview of standard needle EMG as well as discussing advanced recording and analysis techniques and their increasing role in clinical research.