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Many patients with medically refractory epilepsy now undergo successful surgery based on noninvasive diagnostic information, but intracranial electroencephalography ( IEEG) continues to be used as increasingly complex cases are considered surgical candidates. The indications for IEEG and the modalities employed vary across epilepsy surgical centers; each modality has its advantages and limitations. IEEG can be performed in the same intraoperative setting, that is, intraoperative electrocorticography, or through an independent implantation procedure with chronic extraoperative recordings; the latter are not only resource intensive but also carry risk. A lack of understanding of IEEG limitations predisposes to data misinterpretation that can lead to denying surgery when indicated or, worse yet, incorrect resection with adverse outcomes. Given the lack of class 1 or 2 evidence on IEEG, a consensus-based expert recommendation on the diagnostic utility of IEEG is presented, with emphasis on the application of various modalities in specific substrates or locations, taking into account their relative efficacy, safety, ease, and incremental cost-benefit. These recommendations aim to curtail outlying indications that risk the over- or underutilization of IEEG, while retaining substantial flexibility in keeping with most standard practices at epilepsy centers and addressing some of the needs of resource-poor regions around the world. [ABSTRACT FROM AUTHOR]

Objective Although a clear correlation has been observed between high-frequency oscillations ( HFOs) and the seizure-onset zone in distinct lesions, the role of the underlying pathologic substrates in the generation of HFOs is not well established. We aimed to investigate HFO correlates of different pathologic substrates in patients with drug-resistant epilepsy, and to examine the relation of HFOs with the anatomic location of the dysplastic lesion and surrounding tissue in patients with focal cortical dysplasia ( FCD). Methods We studied consecutive patients with drug-resistant epilepsy who underwent intracranial electroencephalography ( iEEG) investigations with depth electrodes at the Montreal Neurological Institute and Hospital, between November 2004 and May 2013. Inclusion criteria were the following: a focal lesion documented by magnetic resonance imaging ( MRI); EEG recording at a 2,000 Hz sampling rate; and seizures starting from depth electrode contacts placed in lesion and perilesional tissue. Results Thirty-seven patients (13 FCD, 12 mesial temporal sclerosis, five cortical atrophy, three polymicrogyria, three nodular heterotopia, and one tuberous sclerosis) were included; 18 were women (median age 34). Ripples and fast ripples were found in all lesion types, except tuberous sclerosis, which showed no fast ripples. There was a significant difference in rates of ripples and fast ripples across different lesions (p < 0.001), with higher rates in FCD, mesial temporal sclerosis, and nodular heterotopia than in atrophy, polymicrogyria, and tuberous sclerosis. Regarding patients with FCD, HFOs rates differed significantly across the three types of tissue (lesional, perilesional, and nonlesional; p < 0.001), being higher within the borders of the MRI-visible dysplastic lesion, followed by the surrounding area, and rare in the remote cortex. Significance Our findings suggest that in patients who are all intractable, the HFO rates vary with different pathologies, and reflect different types of neuronal derangements. Our results also emphasize the potential usefulness of HFOs as an additional method to better define the extent of the epileptogenic dysplastic tissue in FCD. [ABSTRACT FROM AUTHOR]

Purpose: Many recent studies have reported the importance of high-frequency oscillations (HFOs) in the intracerebral electroencephalography (EEG) of patients with epilepsy. These HFOs have been defined as events that stand out from the background. We have noticed that this background often consists itself of high-frequency rhythmic activity. The purpose of this study is to perform a first evaluation of the characteristics of high-frequency continuous or semicontinuous background activity. Methods: Because the continuous high-frequency pattern was noted mainly in mesial temporal structures, we reviewed the EEG studies from these structures in 24 unselected patients with electrodes implanted in these regions. Sections of background away from interictal spikes were marked visually during periods of slow-wave sleep and wakefulness. They were then high-passed filtered at 80 Hz and categorized as having high-frequency rhythmic activity in one of three patterns: continuous/semicontinuous, irregular, sporadic. Wavelet entropy, which measures the degree of rhythmicity of a signal, was calculated for the marked background sections. Key Findings: Ninety-six bipolar channels were analyzed. The continuous/semicontinuous pattern was found frequently (29/96 channels during wake and 34/96 during sleep). The different patterns were consistent between sleep and wakefulness. The continuous/semicontinuous pattern was found significantly more often in the hippocampus than in the parahippocampal gyrus and was rarely found in the amygdala. The types of pattern were not influenced by whether a channel was within the seizure-onset zone, or whether it was a lesional channel. The continuous/semicontinuous pattern was associated with a higher frequency of spikes and with high rates of ripples and fast ripples. Significance: It appears that high-frequency activity (above 80 Hz) does not appear only in the form of brief paroxysmal events but also in the form of continuous rhythmic activity or very long bursts. In this study limited to mesial temporal structures, we found a clear anatomic preference for the hippocampus. Although associated with spikes and with distinct HFOs, this pattern was not clearly associated with the seizure-onset zone. Future studies will need to evaluate systematically the presence of this pattern, as it may have a pathophysiologic significance and it will also have an important influence on the very definition of HFOs. [ABSTRACT FROM AUTHOR]

Idiopathic generalized epilepsy (IGE) is characterized by electroencephalography (EEG) recordings with generalized spike wave discharges (GSWDs) arising from normal background activity. Although GSWDs are the result of highly synchronized activity in the thalamocortical network, EEG without GSWDs is believed to represent normal brain activity. The aim of this study was to investigate whether thalamocortical interactions are altered even during GSWD-free EEG periods in patients with IGE. A GSWD-related group analysis was performed in 12 IGE patients to define seeds in areas involved during GSWDs. EEG-functional magnetic resonance imaging (fMRI) datasets from 22 IGE patients without GSWDs during the investigation and 30 age-matched healthy controls were then selected to investigate functional connectivity in GSWD-related areas. Blood oxygen level dependent (BOLD) signal changes were extracted from seeds defined by the GSWD-related group analysis. The averaged time course within each seed was used to detect brain regions with BOLD signal correlated with the seed. Group differences between patients and controls were estimated. The GSWD-related group analysis showed BOLD activation in the thalamus, the frontomesial cortex, and the cerebellum and BOLD deactivation in default mode areas. For the connectivity analysis, eight seeds were placed bilaterally in the thalamus, mesial frontal cortex, precuneus, and cerebellum. The functional connectivity analysis of these seeds did not show clearly altered functional connectivity for patients versus controls. The results underscore the paroxysmal nature of GSWDs: Although GSWDs are characterized by highly synchronized activity in the thalamocortical network, the functional connectivity in areas involved during GSWDs does not demonstrate abnormality in GSWD-free periods. [ABSTRACT FROM AUTHOR]

Absences are characterized by an abrupt onset and end of generalized 3-4 Hz spike and wave discharges (GSWs), accompanied by unresponsiveness. Although previous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) studies showed that thalamus, default mode areas, and caudate nuclei are involved in absence seizures, the contribution of these regions throughout the ictal evolution of absences remains unclear. Furthermore, animal models provide evidence that absences are initiated by a cortical focus with a secondary involvement of the thalamus. The aim of this study was to investigate dynamic changes during absences. Seventeen absences from nine patients with absence epilepsy and classical pattern of 3-4 Hz GSWs during EEG-fMRI recording were included in the study. The absences were studied in a sliding window analysis, providing a temporal sequence of blood oxygen-level dependent (BOLD) response maps. Thalamic activation was found in 16 absences (94%), deactivation in default mode areas in 15 (88%), deactivation of the caudate nuclei in 10 (59%), and cortical activation in patient-specific areas in 10 (59%) of the absences. Cortical activations and deactivations in default mode areas and caudate nucleus occurred significantly earlier than thalamic responses. Like a fingerprint, patient-specific BOLD signal changes were remarkably consistent in space and time across different absences of one patient but were quite different from patient to patient, despite having similar EEG pattern and clinical semiology. Early frontal activations could support the cortical focus theory, but with an addition: This early activation is patient specific. [ABSTRACT FROM AUTHOR]

Purpose: In simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), increased neuronal activity from epileptiform spikes commonly elicits positive blood oxygenation level–dependent (BOLD) responses. Negative responses are also occasionally seen and have not been explained. Recent studies describe BOLD signal changes before focal EEG spikes. We aimed to systematically study if the undershoot of a preceding positive response might explain the negative BOLD seen in the focus. Methods: Eighty-two patients with focal epilepsy who underwent EEG-fMRI at 3T were retrospectively studied. Studies with a focal negative BOLD response in the region of the spike field were reanalyzed using models with hemodynamic response functions (HRFs) peaking from −9 to +9 s around the spike. Results: Eight patients met the inclusion criteria, showing negative BOLD responses in the spike field on standard analysis. None had positive BOLD responses immediately adjacent to the areas of deactivation. Regions of deactivation were found to have congruent preceding positive responses in two cases. These early activations were seen at the combined maps of −5 to −9 s. Discussion: This study indicates that in a small proportion of patients with focal epilepsy in whom the standard analysis reveals focal negative responses, an earlier positive BOLD response is probably the cause. The origin of negative BOLD signal changes in the focus as a result of an epileptic event remains, however, unexplained in most of the patients in whom it occurs. [ABSTRACT FROM AUTHOR]

Simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) (EEG-fMRI) recording is a noninvasive tool for investigating epileptogenic networks. Most EEG-fMRI studies in epilepsy have been performed in adults. Childhood epilepsies, however, differ from those in adults due to interactions between epileptogenic and developmental processes. The purpose of this study was to investigate EEG-fMRI in children with lesional epilepsies. Thirteen children with symptomatic epilepsy underwent a 20-min EEG-fMRI acquisition at 3 T under sedation-induced sleep. Statistical analysis was performed using the timing of spikes as events, modelled with hemodynamic response functions (HRFs) that peaked at 3, 5, 7, and 9 s after the spike. Each spike type was analyzed separately, resulting in 25 studies. In 84% of the studies, blood oxygenation level-dependent (BOLD) responses were localized in the lesion or brain area presumably generating spikes. Activation (positive BOLD) corresponding with the lesion was seen in 20% and deactivation (negative BOLD) in 52% of the studies. In the area of spike generation, activation was found in 48% of studies and deactivation in 36%. Despite the necessarily short recording times (20 min), good results could be obtained from the EEG-fMRI recordings, performed in sedated children using a high field scanner and individual HRFs. In contrast to studies in adults, deactivations in the lesion and the irritative zone were more common than activations. The impact of age, sleep, and sedation on the BOLD response might explain these findings, but future studies in children should not disregard the importance of deactivations in relation to the epileptogenic network. [ABSTRACT FROM AUTHOR]

Background: Familial partial epilepsy with variable foci (FPEVF) is an autosomal dominant syndrome characterized by partial seizures originating from different brain regions in different family members in the absence of detectable structural abnormalities. A gene for FPEVF was mapped to chromosome 22q12 in two distantly related French-Canadian families. Methods: We describe the clinical features and performed a linkage analysis in a Spanish kindred and in a third French-Canadian family distantly related to the original pedigrees. Results: Onset of seizures was typically in middle childhood, and attacks were usually easy to control. Seizure semiology varied among family members but was constant for each individual. In some, a pattern of nocturnal frontal lobe seizures led to consideration of the diagnosis of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The Spanish family was mapped to chromosome 22q (multipoint lod score, 3.4), and the new French-Canadian family had a multipoint lod score of 2.97 and shared the haplotype of the original French-Canadian families. Conclusions: Identification of the various forms of familial partial epilepsy is challenging, particularly in small families, in which insufficient individuals exist to identify a specific pattern. We provide clinical guidelines for this task, which will eventually be supplanted by specific molecular diagnosis. We confirmed linkage of FPEVF to chromosome 22q12 and redefined the region to a 5.2-Mb segment of DNA. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical characteristics and surgical outcomes in patients with unilateral hippocampal sclerosis whose scalp ictal EEG recordings localize to the opposite temporal lobe. Methods: We retrospectively reviewed the data of all adult patients who had undergone depth electrode implantation for suspected temporal lobe epilepsy (TLE) at UCLA (1993–2000) or the Montreal Neurological Institute (1991–1998) to identify patients who had (a) unilateral hippocampal atrophy, and (b) surface ictal recordings in which the majority of seizures appeared to initiate in the opposite temporal lobe, with few or none that were concordant with the hippocampal atrophy. Results: Of 109 patients with suspected TLE who underwent depth electrode study at the two centers, five patients met the aforementioned criteria. Four of these five had very severe hippocampal atrophy, whereas the fifth had mild atrophy but extensive signal change on magnetic resonance imaging (MRI). Depth electrode recordings in four of the five patients yielded clear ictal onset in the mesial temporal lobe ipsilateral to the imaging abnormality (contralateral to apparent scalp ictal onset). One patient had an unusual bitemporal onset pattern, which was nonetheless suggestive of onset in the sclerotic hippocampus. No patient had intracranial ictal onset contralateral to the imaging abnormality. All patients underwent resection of the structurally abnormal temporal lobe. After follow-up of ≥2 years, four (80%) of five patients were seizure free, while the fifth showed lesser improvement (class III). Conclusions: Some patients with severe hippocampal sclerosis (sometimes called a “burned-out hippocampus”) have atypical spread of ictal discharges, resulting in apparent gross discordance between imaging and scalp ictal recordings. These patients nonetheless have excellent surgical outcomes on the whole. Whether such patients may forego intracranial recordings requires further study. [ABSTRACT FROM AUTHOR]

Purpose: The role of posterior structural lesions leading to inadequate results after inferomesial temporal resection is well recognized. Here we present poor surgical outcome in six patients with nonlesional intractable epilepsy, well-defined focal anterior and inferomesial temporal epileptic discharges, and posterior temporoparietal symptoms. Methods: We reviewed patient data including scalp video-EEG telemetry, intracranial EEG recording, magnetic resonance imaging (MRI) sequences (1.5 Tesla), and single-photon emission computed tomography (SPECT) findings. Results: Ictal onset was uni- or bilateral diffuse with late preponderance over one temporal, or centrotemporoparietal regions. Four patients had preresection intracranial EEG monitoring, which suggested an epileptogenic zone in the posterior temporal and inferior parietal area in two, in the temporal lobe in one, and was inconclusive in the remaining one, who showed late epileptiform activity in the temporal neocortex. A second intracranial implantation was performed in three of them after a first anterior temporal resection. This led to posterior temporal neocortical localization in two and posterior temporal–inferior parietal localization in one. Including subpial transection, these six patients had one to four operations each, but only limited improvement occurred as a result of surgery in this group of individuals. Conclusions: We conclude that anterior and inferomesial interictal epileptiform temporal discharges and at times even intracranial EEG monitoring may be misleading. Anteromesial temporal resection is ineffective in patients with posterior temporoparietal clinical ictal features. [ABSTRACT FROM AUTHOR]

Summary: Purpose: We investigated possible cognitive effects of topiramate (TPM) in polypharmacy on patients with intractable epilepsy. Methods: Study 1 evaluated 22 consecutively admitted patients whose antiepileptic drugs (AEDs) on admission to the Montreal Neurological Hospital included TPM. Performance on neuropsychological tests administered on and subsequently off TPM was analyzed. Four patients also were tested before taking TPM, allowing comparisons off, then on, and then off the drug again. Measures included intellectual function, verbal and nonverbal memory, language, word and design fluency, somatosensory sensitivity, and motor skills. In Study 2, 16 patients at the Minnesota Epilepsy Group were tested first off, then on TPM with nine cognitive tasks that measured concentration, verbal fluency, language, and psychomotor speed. Results: In Study 1, significant (p ≤ 0.01) improvements were observed off TPM on 13 measures including verbal and nonverbal fluency and certain verbal and perceptual tasks. Notably, verbal learning and memory were unaffected; a limited effect was observed on nonverbal memory. Patients tested 3 times scored better in both tests off TPM compared with on this drug. In Study 2, declines on TPM were observed on all measures, significantly (p ≤ 0.05) for tests of fluency, sustained concentration, and visual motor processing speed. Conclusions: TPM was associated with declines in fluency, attention/concentration, processing speed, language skills, and perception; working memory but not retention was affected. As the two studies used an opposite order of testing on versus off TPM, our results clearly show a performance decrement while patients are taking TPM, without respect to which condition is tested first. [ABSTRACT FROM AUTHOR]

Summary: Valproate (VPA) is an effective, widely used antiepileptic drug. Unfortunately its use in pregnant women is associated with neural tube defects in the offspring. Although the etiology of neural tube defects is multifactorial, there is evidence that underlying genetic susceptibility plays a part. We describe two women taking moderate doses of VPA who repeatedly bore children with neural tube defects, despite folate supplementation. This suggests a pharmacogenetic susceptibility to the teratogenic effects of VPA. [ABSTRACT FROM AUTHOR]