Irena Doležalová

Intracranial EEG seizure onset patterns in unilateral temporal lobe epilepsy and their relationship to other variables

OBJECTIVE We performed a retrospective study to determine the different types of seizure onset patterns (SOP) in invasive EEG (IEEG) in patients with temporal lobe epilepsy (TLE). METHODS We analyzed a group of 51 patients (158 seizures) with TLE who underwent IEEG. We analyzed the dominant frequency during the first 3s after the onset of ictal activity. The cut-off value for distinguishing between fast and slow frequencies was 8 Hz. We defined three types of SOPs: (1) fast ictal activity (FIA) - frequency ≥8 Hz; (2) slow ictal activity (SIA) - frequency <8 Hz; and (3) attenuation of background activity (AT) - no clear-cut rhythmic activity during the first 3s associated with changes of IEEG signal (increase of frequency, decrease of amplitude). We tried to find the relationship between different SOP types and surgery outcome, histopathological findings, and SOZ localization. RESULTS The most frequent SOP was FIA, which was present in 67% of patients. More patients with FIA were classified postoperatively as Engel I than those with SIA and AT (85% vs. 31% vs. 0) (P < 0.001). There were no statistically significant differences in the type of SOP, in the histopathological findings, or in the SOZ localization. CONCLUSION In patients with refractory TLE, seizure onset frequencies ≥8 Hz during the first 3s of ictal activity are associated with a better surgical outcome than frequencies <8 Hz. SIGNIFICANCE Our study suggests that very early seizure onset frequencies in IEEG in patients with TLE could be the independent predictive factor for their outcome, regardless of the localization and etiology.

High-Frequency Oscillations in the Human Anterior Nucleus of the Thalamus

Deep brain stimulation of the anterior nucleus of the thalamus (ANT- DBS) has recently been introduced in therapy for refractory epilepsy and is approved for clinical use in Europe. ANT is a part of the Papez circuitry and is a key structure in the intrathalamic pathways; it also projects to the cingulate gyrus and further to the limbic structures and wide regions of the neocortex, and via the mammillary circuit to the brain stem. ANT stimulation produces EEG changes in the frontal and temporal areas and inhibits seizures. The role played by the ANT in human epileptic seizures and the mechanisms leading to the anti- seizure effects of ANT-DBS have not yet been fully elucidated. Knowledge of processes occurring in the ANT in human epilepsy might improve the understanding of its role. Here we report the first description of interictal and ictal EEG recording in the human ANT.

Frequency-independent characteristics of high-frequency oscillations in epileptic and non-epileptic regions.

OBJECTIVE The purpose of the presented study is to determine whether there are frequency-independent high-frequency oscillation (HFO) parameters which may differ in epileptic and non-epileptic regions. METHODS We studied 31 consecutive patients with medically intractable focal (temporal and extratemporal) epilepsies who were examined by either intracerebral or subdural electrodes. Automated detection was used to detect HFO. The characteristics (rate, amplitude, and duration) of HFO were statistically compared within three groups: the seizure onset zone (SOZ), the irritative zone (IZ), and areas outside the IZ and SOZ (nonSOZ/nonIZ). RESULTS In all patients, fast ripples (FR) and ripples (R) were significantly more frequent and shorter in the SOZ than in the nonSOZ/nonIZ region. In the group of patients with favorable surgical outcomes, the relative amplitude of FR was higher in the SOZ than in the IZ and nonIZ/nonSOZ regions; in patients with poor outcomes, the results were reversed. The relative amplitude of R was significantly higher in the SOZ, with no difference between patients with poor and favorable surgical outcomes. CONCLUSIONS FR are more frequent, shorter, and have higher relative amplitudes in the SOZ area than in other regions. The study suggests a worse prognosis in patients with higher amplitudes of FR outside the SOZ. SIGNIFICANCE Various HFO parameters, especially of FR, differ in epileptic and non-epileptic regions. The amplitude and duration may be as important as the frequency band and rate of HFO in marking the seizure onset region or the epileptogenic area and may provide additional information on epileptogenicity.

Effect of partial drug withdrawal on the lateralization of interictal epileptiform discharges and its relationship to surgical outcome in patients with hippocampal sclerosis

OBJECTIVE To assess changes in the relative lateralization of interictal epileptiform discharges (IEDs) and interictal EEG prognostic value in terms of surgical outcome between periods with full medication (FMP) and reduced medication (RMP) in patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS). METHODS Interictal scalp EEGs of 43 patients were evaluated for the presence of IEDs separately in a waking state (WS) and sleeping state (SS) during FMP and RMP. In each period, patients were categorized as having unitemporal or bitemporal IEDs. Surgical outcome was classified at year 1 after surgery and at last follow-up visit as Engel I or Engel II-IV; and alternatively as completely seizure-free or not seizure-free. RESULTS There were significant changes in relative IED lateralization between FMP and RMP during SS. The representation of patients with unitemporal IEDs declined from 37 (86%) in FMP during SS to 25 (58%) in RMP during SS (p=0.003). At year 1 after surgery, the relative IED lateralization is a predictive factor for surgical outcome defined as Engel I vs. Engel II-IV in both FMP during WS (p=0.037) and during SS (p=0.007), and for surgical outcome defined as completely seizure-free vs. not seizure-free in FMP during SS (p=0.042). At last follow up visit, the relative IED lateralization is a predictor for outcome defined as Engel I vs. Engel II-IV in FMP during SS (p=0.020), and for outcome defined as completely seizure-free vs. not seizure-free in both FMP during WS (p=0.043) and in FMP during SS (p=0.015). When stepwise logistic regression analysis was applied, only FMP during SS was found to be an independent predictor for surgical outcome at year 1 after surgery (completely seizure-free vs. not seizure-free p=0.032, Engel I vs. Engel II-IV p=0.006) and at last follow-up visit (completely seizure-free vs. not seizure-free p=0.024, Engel I vs. Engel II-IV p=0.017). Gender was found to be independent predictor for surgical efficacy at year 1 if the outcome was defined as completely seizure-free vs. not seizure-free (p=0.036). CONCLUSION The predictive value of relative IED lateralization with respect to surgical outcome in interictal EEG is present only during FMP; the predictive value decreases with the reduction of AEDs caused by the change of relative IED lateralization.

Atlas of the normal intracranial electroencephalogram: neurophysiological awake activity in different cortical areas

In contrast to scalp EEG, our knowledge of the normal physiological intracranial EEG activity is scarce. This multicentre study provides an atlas of normal intracranial EEG of the human brain during wakefulness. Here we present the results of power spectra analysis during wakefulness. Intracranial electrodes are placed in or on the brain of epilepsy patients when candidates for surgical treatment and non-invasive approaches failed to sufficiently localize the epileptic focus. Electrode contacts are usually in cortical regions showing epileptic activity, but some are placed in normal regions, at distance from the epileptogenic zone or lesion. Intracranial EEG channels defined using strict criteria as very likely to be in healthy brain regions were selected from three tertiary epilepsy centres. All contacts were localized in a common stereotactic space allowing the accumulation and superposition of results from many subjects. Sixty-second artefact-free sections during wakefulness were selected. Power spectra were calculated for 38 brain regions, and compared to a set of channels with no spectral peaks in order to identify significant peaks in the different regions. A total of 1785 channels with normal brain activity from 106 patients were identified. There were on average 2.7 channels per cm3 of cortical grey matter. The number of contacts per brain region averaged 47 (range 6-178). We found significant differences in the spectral density distributions across the different brain lobes, with beta activity in the frontal lobe (20-24 Hz), a clear alpha peak in the occipital lobe (9.25-10.25 Hz), intermediate alpha (8.25-9.25 Hz) and beta (17-20 Hz) frequencies in the parietal lobe, and lower alpha (7.75-8.25 Hz) and delta (0.75-2.25 Hz) peaks in the temporal lobe. Some cortical regions showed a specific electrophysiological signature: peaks present in >60% of channels were found in the precentral gyrus (lateral: peak frequency range, 20-24 Hz; mesial: 24-30 Hz), opercular part of the inferior frontal gyrus (20-24 Hz), cuneus (7.75-8.75 Hz), and hippocampus (0.75-1.25 Hz). Eight per cent of all analysed channels had more than one spectral peak; these channels were mostly recording from sensory and motor regions. Alpha activity was not present throughout the occipital lobe, and some cortical regions showed peaks in delta activity during wakefulness. This is the first atlas of normal intracranial EEG activity; it includes dense coverage of all cortical regions in a common stereotactic space, enabling direct comparisons of EEG across subjects. This atlas provides a normative baseline against which clinical EEGs and experimental results can be compared. It is provided as an open web resource (https://mni-open-ieegatlas. RESEARCH mcgill.ca).

Differences between mesial and neocortical magnetic-resonance-imaging-negative temporal lobe epilepsy

OBJECTIVE The aim of this study was to assess clinical and electrophysiological differences within a group of patients with magnetic-resonance-imaging-negative temporal lobe epilepsy (MRI-negative TLE) according to seizure onset zone (SOZ) localization in invasive EEG (IEEG). METHODS According to SOZ localization in IEEG, 20 patients with MRI-negative TLE were divided into either having mesial SOZ-mesial MRI-negative TLE or neocortical SOZ-neocortical MRI-negative TLE. We evaluated for differences between these groups in demographic data, localization of interictal epileptiform discharges (IEDs), and the ictal onset pattern in semiinvasive EEG and in ictal semiology. RESULTS Thirteen of the 20 patients (65%) had mesial MRI-negative TLE and 7 of the 20 patients (35%) had neocortical MRI-negative TLE. The differences between mesial MRI-negative TLE and neocortical MRI-negative TLE were identified in the distribution of IEDs and in the ictal onset pattern in semiinvasive EEG. The patients with neocortical MRI-negative TLE tended to have more IEDs localized outside the anterotemporal region (p=0.031) and more seizures without clear lateralization of ictal activity (p=0.044). No other differences regarding demographic data, seizure semiology, surgical outcome, or histopathological findings were found. CONCLUSIONS According to the localization of the SOZ, MRI-negative TLE had two subgroups: mesial MRI-negative TLE and neocortical MRI-negative TLE. The groups could be partially distinguished by an analysis of their noninvasive data (distribution of IEDs and lateralization of ictal activity). This differentiation might have an impact on the surgical approach.

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.

Predictive value of preoperative statistical parametric mapping of regional glucose metabolism in mesial temporal lobe epilepsy with hippocampal sclerosis

OBJECTIVE This study was designed to use statistical parametric mapping of interictal positron-emission tomography using [18F]Fluorodeoxyglucose (FDG-PET) to compare the brain metabolisms of patients with mesial temporal lobe epilepsy (MTLE)/hippocampal sclerosis and controls. Another aim of this study was to analyze the potential differences among patients in terms of epilepsy duration, side of hippocampal sclerosis, histopathological findings, insult in their history, and postoperative outcomes. METHODS We analyzed FDG-PET scans from 49 patients with MTLE/hippocampal sclerosis and 24 control subjects. We analyzed the differences in regional glucose metabolism between the patients and the control group and within the patient group using multiple variables. RESULTS We observed widespread hypometabolism in the patient group in comparison with the control group in temporal and extratemporal areas on the epileptogenic side (ES). On the nonepileptogenic side (NES), we observed the most hypometabolism in the thalamus and the anterior and middle cingulate gyrus. In the group of patients with more severe hippocampal sclerosis, we observed statistically significant hypometabolism in the insula on the ES. In patients with poor postoperative outcomes, we found statistically significant hypometabolism in the insula on the ES and the temporal pole (TP) on the NES. Patients with any insult in their history showed hypermetabolism in the TP on both sides. CONCLUSION Our study showed that there are widespread changes in metabolism in patients with MTLE in comparison to controls, either inside or outside the temporal lobe. There are significant differences among these patients in terms of postoperative outcomes, degree of hippocampal sclerosis, and insults in their history.

Temporal lobe epilepsy? Things are not always what they seem

Temporal lobe epilepsy is the most frequent form of drug-resistant epilepsy referred to epilepsy surgery centres. The vast majority of lesional cases can be operated on without invasive investigation which is often not the case for non-lesional cases. Invasive investigation in non-lesional cases, however, may lead to unexpected results, as illustrated in the following case report. [Published with video sequence on www.epilepticdisorders.com].

Single-center long-term results of vagus nerve stimulation for epilepsy: A 10–17 year follow-up study

PURPOSE The paper presents a long-term follow-up study of VNS patients, analyzing seizure outcome, medication changes, and surgical problems. METHOD 74 adults with VNS for 10 to 17 years were evaluated yearly as: non-responder - NR (seizure frequency reduction <50%), responder - R (reduction ≥ 50% and <90%), and 90% responder - 90R (reduction ≥ 90%). Delayed R or 90R (≥ 4 years after surgery), patients with antiepileptic medication changes and battery or complete system replacement were identified. Statistical analysis of potential outcome predictors (age, seizure duration, MRI, seizure type) was performed. RESULTS The rates of R and 90R related to the patients with outcome data available for the study years 1, 2, 10, and 17 were for R 38.4%, 51.4%, 63.6%, and 77.8%, and for 90R 1.4%, 5.6%, 15.1%, and 11.1%. The absolute numbers of R and 90R increased until years 2 and 6. Antiepileptic therapy was changed in 62 patients (87.9%). There were 11 delayed R and four delayed 90R, with medication changes in the majority. At least one battery replacement was performed in 51 patients (68.9%), 49 of whom R or 90R. VNS system was completely replaced in 7 patients (9.5%) and explanted in 7 NR (9.5%). No significant predictor of VNS outcome was found. CONCLUSIONS After an initial increase, the rate of R and 90R remains stable in long-term follow-up. The changes of antiepileptic treatment in most patients potentially influence the outcome. Battery replacements or malfunctioning system exchange reflect the patients satisfaction and correlate with good outcomes.