The effect of propofol on effective brain networks.

OBJECTIVE: We compared the effective networks derived from Single Pulse Electrical Stimulation (SPES) in intracranial electrocorticography (ECoG) of awake epilepsy patients and while under general propofol-anesthesia to investigate the effect of propofol on these brain networks. METHODS: We included nine patients who underwent ECoG for epilepsy surgery evaluation. We performed SPES when the patient was awake (SPES-clinical) and repeated this under propofol-anesthesia during the surgery in which the ECoG grids were removed (SPES-propofol). We detected the cortico-cortical evoked potentials (CCEPs) with an automatic detector. We constructed two effective networks derived from SPES-clinical and SPES-propofol. We compared three network measures (indegree, outdegree and betweenness centrality), the N1-peak-latency and amplitude of CCEPs between the two effective networks. RESULTS: Fewer CCEPs were observed during SPES-propofol (median: 6.0, range: 0-29) compared to SPES-clinical (median: 10.0, range: 0-36). We found a significant correlation for the indegree, outdegree and betweenness centrality between SPES-clinical and SPES-propofol (respectively rs = 0.77, rs = 0.70, rs = 0.55, p < 0.001). The median N1-peak-latency increased from 22.0 ms during SPES-clinical to 26.4 ms during SPES-propofol. CONCLUSIONS: Our findings suggest that the number of effective network connections decreases, but network measures are only marginally affected. SIGNIFICANCE: The primary network topology is preserved under propofol.

[Awareness during focal epileptic seizures]. / Bewust van kleine epileptische aanvallen.

Not all epileptic seizures are accompanied by loss of awareness. Focal aware seizures provide an opportunity to predict the location of the epileptic source in the brain. The impact of these seizures is often underestimated, especially if someone has previously had seizures with loss of awareness.

Electro-clinical criteria and surgical outcome: Is there a difference between mesial and lesional temporal lobe epilepsy?

OBJECTIVES: Mesial temporal lobe epilepsy syndrome (MTLE) with specific electrophysiological and clinical characteristics and hippocampal sclerosis (HS) on MRI is considered the prototype of a syndrome with good surgical prognosis. Ictal onset zones in MTLE have been found to extend outside the hippocampus and neocortical seizures often involve mesial structures. It can, thus, be questioned whether MTLE with HS is different from lesional temporal epilepsies with respect to electro-clinical characteristics and surgical prognosis. We assessed whether MTLE with HS is distinguishable from lesional TLE and which criteria determine surgical outcome. METHODS: People in a retrospective cohort of 389 individuals with MRI abnormalities who underwent temporal lobectomy, were divided into "HS only" or "lesional" TLEs. Twenty-six presented with dual pathology and were excluded from further analysis. We compared surgical outcome and electro-clinical characteristics. RESULTS: Over half (61%) had "HS only." Four electro-clinical characteristics (age at epilepsy onset, febrile seizures, memory dysfunction and contralateral dystonic posturing) distinguished "HS only" from "lesional" TLE, but there was considerable overlap. Seizure freedom 2 years after surgery (Engel class 1) was similar: 67% ("HS only") vs 69% ("lesional" TLE). Neither presence of HS nor electro-clinical criteria was associated with surgical outcome. CONCLUSIONS: Despite small differences in electrophysiological and clinical characteristics between MTLE with HS and lesional TLE, surgical outcomes are similar, indicating that aetiology seems irrelevant in the referral for temporal surgery.

Evoked versus spontaneous high frequency oscillations in the chronic electrocorticogram in focal epilepsy.

OBJECTIVE: Spontaneous high frequency oscillations (HFOs; ripples 80-250Hz, fast ripples (FRs) 250-500Hz) are biomarkers for epileptogenic tissue in focal epilepsy. Single pulse electrical stimulation (SPES) can evoke HFOs. We hypothesized that stimulation distinguishes pathological from physiological ripples and compared the occurrence of evoked and spontaneous HFOs within the seizure onset zone (SOZ) and eloquent functional areas. METHODS: Ten patients underwent SPES during 2048Hz electrocorticography (ECoG). Evoked HFOs in time-frequency plots and spontaneous HFOs were visually analyzed. We compared electrodes with evoked and spontaneous HFOs for: percentages in the SOZ, sensitivity and specificity for the SOZ, percentages in functional areas outside the SOZ. RESULTS: Two patients without spontaneous FRs showed evoked FRs in the SOZ. Percentages of evoked and spontaneous HFOs in the SOZ were similar (ripples 32:33%, p=0.77; FRs 43:48%, p=0.63), but evoked HFOs had generally a lower specificity (ripples 45:69%, p=0.02; FRs 83:92%, p=0.04) and higher sensitivity (ripples 85:70%, p=0.27; FRs 52:37%, p=0.05). More electrodes with evoked than spontaneous ripples were found in functional (54:30%, p=0.03) and 'silent' areas (57:27%, p=0.01) outside the SOZ. CONCLUSIONS: SPES can elicit SOZ-specific FRs in patients without spontaneous FRs, but activates ripples in all areas. SIGNIFICANCE: SPES is an alternative for waiting for spontaneous HFOs, but does not warrant exclusively pathological ripples.

The topographical distribution of epileptic spikes in juvenile myoclonic epilepsy with and without photosensitivity.

OBJECTIVE: Up to 30% of people with juvenile myoclonic epilepsy (JME) have photoparoxysmal responses (PPR). Recent studies report on structural and pathophysiological differences between people with JME with (JME+PPR) and without PPR (JME-PPR). We investigated whether electrophysiological features outside photic stimulation differ between these subtypes. METHODS: We analysed EEG recordings of people with JME at a tertiary epilepsy centre and an academic hospital. Photosensitivity was assessed in a drug-naïve condition. We compared the occurrence and involvement of posterior electrodes for focal abnormalities and generalised spike-wave activity in the EEG outside photic stimulation between JME+PPR and JME-PPR. RESULTS: We included EEG recordings of 18 people with JME+PPR and 21 with JME-PPR. People with JME-PPR had less focal abnormalities in the posterior brain regions than people with JME+PPR (19% vs 55%, p<0.05). There was no difference in the distribution of generalised spike-wave activity between people with JME+PPR and JME-PPR. CONCLUSION: This study demonstrates electrophysiological correlates of the previously described structural and physiological differences between JME+PPR and JME-PPR. SIGNIFICANCE: Findings support the hypothesis that posterior interictal EEG abnormalities reflect localised cortical hyperexcitability, which makes patients with JME more sensitive to photic stimuli.

High frequency oscillations and high frequency functional network characteristics in the intraoperative electrocorticogram in epilepsy.

OBJECTIVE: High frequency oscillations (HFOs; > 80 Hz), especially fast ripples (FRs, 250-500 Hz), are novel biomarkers for epileptogenic tissue. The pathophysiology suggests enhanced functional connectivity within FR generating tissue. Our aim was to determine the relation between brain areas showing FRs and 'baseline' functional connectivity within EEG networks, especially in the high frequency bands. METHODS: We marked FRs, ripples (80-250 Hz) and spikes in the electrocorticogram of 14 patients with refractory temporal lobe epilepsy. We assessed 'baseline' functional connectivity in epochs free of epileptiform events within these recordings, using the phase lag index. We computed the Eigenvector Centrality (EC) per channel in the FR and gamma band network. We compared EC between channels that did or did not show events at other moments in time. RESULTS: FR-band EC was higher in channels with than without spikes. Gamma-band EC was lower in channels with ripples and FRs. CONCLUSIONS: We confirmed previous findings of functional isolation in the gamma-band and found a first proof of functional integration in the FR-band network of channels covering presumed epileptogenic tissue. SIGNIFICANCE: 'Baseline' high-frequency network parameters might help intra-operative recognition of epileptogenic tissue without the need for waiting for events. These findings can increase our understanding of the 'architecture' of epileptogenic networks and help unravel the pathophysiology of HFOs.

Anti-epileptic drug changes and quality of life in the community.

OBJECTIVE: Changes in anti-epileptic drug (AED) regimens may indicate unsatisfactory treatment results such as insufficient seizure control or adverse effects. This inference underlies epilepsy management and research, yet current studies often do not account for AED changes. We assessed AED change patterns and their association with quality of life (QoL), as main outcome measure, in a community-based setting. METHODS: We assessed a cohort of 248 people with epilepsy identified from community pharmacy records from whom we retrieved AED dispensing history. We assessed all changes in AED use during the 2 years prior to the index date and current QoL using the validated Dutch QOLIE-31 questionnaire. RESULTS: Thirty-one per cent had at least one AED change during the study period, either in drug type or dose. People who changed showed significantly lower QoL (QOLIE score 73 vs 79), especially those who intensified their treatment. Each additional change was associated with a further reduction of 4.9 points in QoL score. CONCLUSIONS: AED changes are common practice, even in people with long-standing epilepsy. Frequent changes, as objective measure of epilepsy severity, are associated with a progressively lower QoL. Changes, even in dose, should be monitored in daily clinical practice and used as a red flag that may require adjustments in epilepsy management. This may include earlier referral to a specialized centre for a more thorough evaluation or counselling. AED changes can also be used as an outcome marker in epilepsy research as a proxy of QoL for better translation of drug-efficacy results to general practice.

Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses.

OBJECTIVE: Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical connectivity. We analyzed properties of ERs, including frequencies >80 Hz, in the SOZ and seizure propagation areas. METHODS: We used data from 12 refractory epilepsy patients. SPES consisted of 10 pulses of 1 ms, 4-8 mA and 5s interval on adjacent electrodes pairs. Data were available at 2048 samples/s for six and 512 samples/s (22 bits) for eight patients and analyzed in the time-frequency (TF) and time-domain (TD). RESULTS: Electrodes with ERs were stronger associated with SOZ than non-SOZ electrodes. ERs with frequency content >80 Hz exist and are specific for SOZ channels. ERs evoked by stimulation of seizure onset electrodes were associated with electrodes involved in seizure propagation. CONCLUSION: Analysis of ERs can reveal aspects of pathology, manifested by association with seizure propagation and areas with high ER numbers that coincide with the SOZ. SIGNIFICANCE: Not only DRs, but also ERs could have clinical value for mapping epileptogenic cortex and help to unravel aspects of the epileptic network.

High frequency oscillations in intra-operative electrocorticography before and after epilepsy surgery.

OBJECTIVE: Removal of brain tissue showing high frequency oscillations (HFOs; ripples: 80-250Hz and fast ripples: 250-500Hz) in preresection electrocorticography (preECoG) in epilepsy patients seems a predictor of good surgical outcome. We analyzed occurrence and localization of HFOs in intra-operative preECoG and postresection electrocorticography (postECoG). METHODS: HFOs were automatically detected in one-minute epochs of intra-operative ECoG sampled at 2048Hz of fourteen patients. Ripple, fast ripple, spike, ripples on a spike (RoS) and not on a spike (RnoS) rates were analyzed in pre- and postECoG for resected and nonresected electrodes. RESULTS: Ripple, spike and fast ripple rates decreased after resection. RnoS decreased less than RoS (74% vs. 83%; p=0.01). Most fast ripples in preECoG were located in resected tissue. PostECoG fast ripples occurred in one patient with poor outcome. Patients with good outcome had relatively high postECoG RnoS rates, specifically in the sensorimotor cortex. CONCLUSIONS: Our observations show that fast ripples in intra-operative ECoG, compared to ripples, may be a better biomarker for epileptogenicity. Further studies have to determine the relation between resection of epileptogenic tissue and physiological ripples generated by the sensorimotor cortex. SIGNIFICANCE: Fast ripples in intra-operative ECoG can help identify the epileptogenic zone, while ripples might also be physiological.

Eliciting patients' preferences for epilepsy diagnostics: a discrete choice experiment.

BACKGROUND: Diagnosing epilepsy is a lengthy and burdensome process for patients and their family. Although the need for a more patient-centered approach in clinical practice is widely acknowledged, empirical evidence regarding patient preferences for diagnostic modalities in epilepsy is missing. The objectives of this study were 1) to identify to what extent important attributes of diagnostic procedures in epilepsy affect preferences for a procedure, 2) to determine the relative importance of these attributes, and 3) to calculate overall utility scores for routine electroencephalography (EEG) and magnetoencephalography (MEG) recordings. METHODS: A discrete choice experiment was performed to determine patients' preferences, which involved presentation of pairwise choice tasks regarding hypothetical scenarios. Scenarios varied along six attributes: "way of measuring brain activity", "duration", "freedom of movement", "travel time", "type of additional examination", and "chance of additional examination". Choice tasks were constructed using a statistically efficient design, and the questionnaire contained 15 unique unlabeled choice tasks. Mixed multinomial logistic regression was used to estimate patients' preferences. RESULTS: A total of 289 questionnaires were included in the analysis. McFadden's pseudo R(2) showed a model fit of 0.28, and all attributes were statistically significant. Heterogeneity in preferences was present for all attributes. "Freedom of movement" and "Chance of additional examination" were perceived as the most important attributes. Overall utility scores did not substantially differ between routine EEG and MEG. CONCLUSION: This study suggests that the identified attributes are important in determining patients' preference for epilepsy diagnostics. It can be concluded that MEG is not necessarily more patient-friendly than a routine EEG in primary diagnostics and, regarding additional diagnostics, patients have a strong preference for long-term 24-h EEG over EEG after sleep deprivation. Furthermore, barring substantial heterogeneity within the parameters in mind, our study suggests that it is important to take individual preferences into account in medical decision-making.

Finger snapping during seizures.

We describe two patients who showed snapping of the right hand fingers during invasive intracranial EEG evaluation for epilepsy surgery. We correlated the EEG changes with the finger-snapping movements in both patients to determine the underlying pathophysiology of this phenomenon. At the time of finger snapping, EEG spread from the supplementary motor area towards the temporal region was seen, suggesting involvement of these sites.

Task-free electrocorticography frequency mapping of the motor cortex.

OBJECTIVE: Electrocortical stimulation mapping (ESM) is the current gold standard for functional mapping of the eloquent cortex prior to epilepsy surgery. The procedure is, however, time-consuming and quite demanding for patients. Electrocorticography frequency mapping (ECoG mapping) has been suggested as an adjunct method. Here, we investigated whether it is possible to perform mapping of motor regions using ECoG data of spontaneous movements. METHODS: Using the video registration of seven epilepsy patients who underwent electrocorticography and ESM, we selected periods of spontaneous hand and arm movements and periods of rest. Frequency analysis was performed, and electrodes showing a significant change in power (4-7, 8-14, 15-25, 26-45 or 65-95 Hz) were compared with those being identified as relevant for hand and/or arm movement by ESM. RESULTS: All frequency bands showed a high specificity (>0.80), and the 65-95 Hz frequency band additionally had a high sensitivity (0.82) for identifying ESM positive electrodes. CONCLUSIONS: Our data show a good match between ECoG mapping of spontaneous movements and ESM data. SIGNIFICANCE: The accurate match suggests that ECoG mapping of the motor cortex using spontaneous movements may be a valuable complement to ESM, especially when other options requiring patient cooperation fail.

Frequency specific spatial interactions in human electrocorticography: V1 alpha oscillations reflect surround suppression.

Electrical brain signals are often decomposed into frequency ranges that are implicated in different functions. Using subdural electrocorticography (ECoG, intracranial EEG) and functional magnetic resonance imaging (fMRI), we measured frequency spectra and BOLD responses in primary visual cortex (V1) and intraparietal sulcus (IPS). In V1 and IPS, 30-120 Hz (gamma, broadband) oscillations allowed population receptive field (pRF) reconstruction comparable to fMRI estimates. Lower frequencies, however, responded very differently in V1 and IPS. In V1, broadband activity extends down to 3 Hz. In the 4-7 Hz (theta) and 18-30 Hz (beta) ranges broadband activity increases power during stimulation within the pRF. However, V1 9-12 Hz (alpha) frequency oscillations showed a different time course. The broadband power here is exceeded by a frequency-specific power increase during stimulation of the area outside the pRF. As such, V1 alpha oscillations reflected surround suppression of the pRF, much like negative fMRI responses. They were consequently highly localized, depending on stimulus and pRF position, and independent between nearby electrodes. In IPS, all 3-25 Hz oscillations were strongest during baseline recording and correlated between nearby electrodes, consistent with large-scale disengagement. These findings demonstrate V1 alpha oscillations result from locally active functional processes and relate these alpha oscillations to negative fMRI signals. They highlight that similar oscillations in different areas reflect processes with different functional roles. However, both of these roles of alpha seem to reflect suppression of spiking activity.

The contribution of posterior circulation to memory function during the intracarotid amobarbital procedure.

The purpose of this study was to evaluate the contribution of posterior circulation to memory function by comparing memory scores between patients with and without a foetal-type posterior cerebral artery (FTP) during the intracarotid amobarbital procedure (IAP) in epilepsy patients. Patients undergoing bilateral IAP between January 2004 and January 2010 were retrospectively included. Pre-test angiograms were assessed for the presence of a FTP. Memory function scores (% correct) after right and left injections were obtained. Functional significance of FTP was affirmed by relative occipital versus parietal EEG slow-wave increase during IAP. Memory and EEG scores were compared between patients with and without FTP (Mann-Whitney U test). A total of 106 patients were included, 73 with posterior cerebral arteries (PCA) without FTP ('non-FTP'), 28 patients with unilateral FTP and 5 with a bilateral FTP. Memory scores were lower when amytal was injected to the hemisphere contralateral to the presumed seizure focus (on the right decreasing from 98.3 to 59.1, and on the left decreasing from 89.1 to 72.4; p < 0.001). When IAP was performed on the side of FTP memory scores were significantly lower (70.8) compared to non-FTP (82.0; p = 0.02). Relative occipital EEG changes were 0.44 for FTP cases and 0.36 for non-FTP patients (p = 0.01). A relationship between vasculature and brain function was demonstrated by lower memory scores and more slow-wave activity on occipital EEG during IAP in patients with foetal-type PCA compared to patients with non-FTP. This suggests an important contribution of brain areas supplied by the PCA to memory function.

Contralateral MRI abnormalities affect seizure and cognitive outcome after hemispherectomy.

OBJECTIVE: To explore whether EEG and MRI abnormalities in the "healthy" hemisphere influence seizure and cognitive outcome after functional hemispherectomy. METHODS: This is a retrospective consecutive cohort study of 43 children who underwent functional hemispherectomy between 1994 and 2008. Results of preoperative EEG recordings were reviewed for the existence of (inter)ictal epileptic or background abnormalities in the contralateral hemisphere. Preoperative MRIs were reexamined for the existence of unequivocal contralateral abnormalities. Postoperative seizure status was assessed, and of 34 children, IQ or mental developmental index (MDI) scores were obtained preoperatively and postoperatively. Seizure freedom was defined as Engel 1A. Contralateral EEG and MRI abnormalities were studied in relation to seizure and cognitive outcome. RESULTS: Thirty-three children achieved seizure freedom (77%). Of the 11 patients with contralateral MRI abnormalities, only 45% were seizure free, compared with 88% of the 32 patients without contralateral MRI lesions (p = 0.030). Children with contralateral MRI abnormalities more often were severely retarded after surgery (MDI/IQ <55; 90% vs 42%, p = 0.030). Postoperative MDI/IQ scores improved in none of the children with, but in 38% of those without contralateral MRI abnormalities (p = 0.034). Contralateral epileptic or background EEG abnormalities did not affect seizure outcome or postoperative cognitive performance. Four of 6 children with bilateral epileptic encephalopathy reached seizure freedom. CONCLUSION: Unambiguous contralateral MRI abnormalities are significantly associated with seizure recurrence, severe mental delay, and lack of cognitive improvement and may be considered a relative contraindication for hemispherectomy. Contralateral EEG abnormalities do not negatively influence postsurgical outcome.