High-frequency oscillations recorded with surface EEG in neonates with seizures.

OBJECTIVE: Neonatal seizures are often the first symptom of perinatal brain injury. High-frequency oscillations (HFOs) are promising new biomarkers for epileptogenic tissue and can be found in intracranial and surface EEG. To date, we cannot reliably predict which neonates with seizures will develop childhood epilepsy. We questioned whether epileptic HFOs can be generated by the neonatal brain and potentially predict epilepsy. METHODS: We selected 24 surface EEGs sampled at 2048 Hz with 175 seizures from 16 neonates and visually reviewed them for HFOs. Interictal epochs were also reviewed. RESULTS: We found HFOs in thirteen seizures (7%) from four neonates (25%). 5025 ictal ripples (rate 10 to 1311/min; mean frequency 135 Hz; mean duration 66 ms) and 1427 fast ripples (rate 8 to 356/min; mean frequency 298 Hz; mean duration 25 ms) were marked. Two neonates (13%) showed interictal HFOs (285 ripples and 25 fast ripples). Almost all HFOs co-occurred with sharp transients. We could not find a relationship between neonatal HFOs and outcome yet. CONCLUSIONS: Neonatal HFOs co-occur with ictal and interictal sharp transients. SIGNIFICANCE: The neonatal brain can generate epileptic ripples and fast ripples, particularly during seizures, though their occurrence is not common and potential clinical value not evident yet.

A machine-learning algorithm for neonatal seizure recognition: a multicentre, randomised, controlled trial.

BACKGROUND: Despite the availability of continuous conventional electroencephalography (cEEG), accurate diagnosis of neonatal seizures is challenging in clinical practice. Algorithms for decision support in the recognition of neonatal seizures could improve detection. We aimed to assess the diagnostic accuracy of an automated seizure detection algorithm called Algorithm for Neonatal Seizure Recognition (ANSeR). METHODS: This multicentre, randomised, two-arm, parallel, controlled trial was done in eight neonatal centres across Ireland, the Netherlands, Sweden, and the UK. Neonates with a corrected gestational age between 36 and 44 weeks with, or at significant risk of, seizures requiring EEG monitoring, received cEEG plus ANSeR linked to the EEG monitor displaying a seizure probability trend in real time (algorithm group) or cEEG monitoring alone (non-algorithm group). The primary outcome was diagnostic accuracy (sensitivity, specificity, and false detection rate) of health-care professionals to identify neonates with electrographic seizures and seizure hours with and without the support of the ANSeR algorithm. Neonates with data on the outcome of interest were included in the analysis. This study is registered with ClinicalTrials.gov, NCT02431780. FINDINGS: Between Feb 13, 2015, and Feb 7, 2017, 132 neonates were randomly assigned to the algorithm group and 132 to the non-algorithm group. Six neonates were excluded (four from the algorithm group and two from the non-algorithm group). Electrographic seizures were present in 32 (25·0%) of 128 neonates in the algorithm group and 38 (29·2%) of 130 neonates in the non-algorithm group. For recognition of neonates with electrographic seizures, sensitivity was 81·3% (95% CI 66·7-93·3) in the algorithm group and 89·5% (78·4-97·5) in the non-algorithm group; specificity was 84·4% (95% CI 76·9-91·0) in the algorithm group and 89·1% (82·5-94·7) in the non-algorithm group; and the false detection rate was 36·6% (95% CI 22·7-52·1) in the algorithm group and 22·7% (11·6-35·9) in the non-algorithm group. We identified 659 h in which seizures occurred (seizure hours): 268 h in the algorithm versus 391 h in the non-algorithm group. The percentage of seizure hours correctly identified was higher in the algorithm group than in the non-algorithm group (177 [66·0%; 95% CI 53·8-77·3] of 268 h vs 177 [45·3%; 34·5-58·3] of 391 h; difference 20·8% [3·6-37·1]). No significant differences were seen in the percentage of neonates with seizures given at least one inappropriate antiseizure medication (37·5% [95% CI 25·0 to 56·3] vs 31·6% [21·1 to 47·4]; difference 5·9% [-14·0 to 26·3]). INTERPRETATION: ANSeR, a machine-learning algorithm, is safe and able to accurately detect neonatal seizures. Although the algorithm did not enhance identification of individual neonates with seizures beyond conventional EEG, recognition of seizure hours was improved with use of ANSeR. The benefit might be greater in less experienced centres, but further study is required. FUNDING: Wellcome Trust, Science Foundation Ireland, and Nihon Kohden.

Characterisation of neonatal seizures and their treatment using continuous EEG monitoring: a multicentre experience.

OBJECTIVE: The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres. METHODS: Neonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server. RESULTS: Of 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9-51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11-32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED. CONCLUSIONS: Our results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat. OBERSERVATION STUDY NUMBER: NCT02160171.

Rhythmic EEG patterns in extremely preterm infants: Classification and association with brain injury and outcome.

OBJECTIVE: Classify rhythmic EEG patterns in extremely preterm infants and relate these to brain injury and outcome. METHODS: Retrospective analysis of 77 infants born <28 weeks gestational age (GA) who had a 2-channel EEG during the first 72 h after birth. Patterns detected by the BrainZ seizure detection algorithm were categorized: ictal discharges, periodic epileptiform discharges (PEDs) and other waveforms. Brain injury was assessed with sequential cranial ultrasound (cUS) and MRI at term-equivalent age. Neurodevelopmental outcome was assessed with the BSITD-III (2 years) and WPPSI-III-NL (5 years). RESULTS: Rhythmic patterns were observed in 62.3% (ictal 1.3%, PEDs 44%, other waveforms 86.3%) with multiple patterns in 36.4%. Ictal discharges were only observed in one and excluded from further analyses. The EEG location of the other waveforms (p<0.05), but not PEDs (p=0.238), was significantly associated with head position. No relation was found between the median total duration of each pattern and injury on cUS and MRI or cognition at 2 and 5 years. CONCLUSIONS: Clear ictal discharges are rare in extremely preterm infants. PEDs are common but their significance is unclear. Rhythmic waveforms related to head position are likely artefacts. SIGNIFICANCE: Rhythmic EEG patterns may have a different significance in extremely preterm infants.

Epileptic high-frequency oscillations in intraoperative electrocorticography: the effect of propofol.

PURPOSE: Epileptic high-frequency oscillations (HFOs; 80-500 Hz) may be used to guide neurosurgeons during epilepsy surgery to identify epileptogenic tissue. We studied the effect of the anesthetic agent propofol on the occurrence of HFOs in intraoperative electrocorticography (ECoG). METHODS: We selected patients who were undergoing surgery for temporal lobe epilepsy with a standardized electrode grid placement. Intraoperative ECoG was recorded at 2,048 Hz following cessation of propofol. The number and distribution of interictal spikes, ripples (R [80-250 Hz]), and fast ripples (FRs; 250-500 Hz) were analyzed. The amount of events on mesiotemporal channels and lateral neocortical channels were compared between patients with a suspected mesiotemporal and lateral epileptogenic area (Student's t-test), and HFOs were compared with the irritative zone, using correlation between amounts of events per channel, to provide evidence for the epileptic nature of the HFOs. Next, the amount of events within the first minute and the last minute were compared to each other and the change in events over the entire epochs was analyzed using correlation analyses of 10 epochs during the emergence periods (Spearman rank test). We studied whether the duration of HFOs changed over time. The change in events within presumed epileptogenic area was compared to the change outside this area (Student's t-test). Periods of burst suppression and continuous background activity were compared between and within patients (t-test). KEY FINDINGS: Twelve patients were included: five with suspected mesiotemporal epileptogenic area and three with suspected lateral epileptogenic area (and four were "other"). Spikes, ripples, and FRs were related to the suspected epileptogenic areas, and HFO zones were related to the irritative zones. Ripples and FRs increased during emergence from propofol anesthesia (mean number of ripples from first minute-last minute: 61.5-73.0, R = 0.46, p < 0.01; FRs: 3.1-5.7, R = 0.30, p < 0.01) and spikes remained unchanged (80.1-79.9, R = -0.05, p = 0.59). There was a decrease in number of channels with spikes (R = -0.18, p = 0.05), but no change in ripples (R = -0.13, p = 0.16) or FRs (R = 0.11, p = 0.45). There was no change in the durations of HFOs. The amount of HFOs in the presumed epileptogenic areas did not change more than the amount outside the presumed epileptogenic area, whereas spikes paradoxically decreased more within the suspected epileptogenic area. Six patients showing burst-suppression had lower rates of ripples than six other patients with continuous background activity (p = 0.02). No significant difference was found between burst suppression and continuous background activity in four patients, but there was a trend toward showing more ripples during continuous background activity (p = 0.16). SIGNIFICANCE: Propofol, known for its antiepileptic effects, reduces the number of epileptic HFOs, but has no effect on spikes. This enforces the hypothesis that, in epilepsy, HFOs mirror the disease activity and HFOs might be useful for monitoring antiepileptic drug treatment. It is feasible to record HFOs during surgery, but propofol infusion should be interrupted for some minutes to improve detection.

Identification of the epileptogenic zone in patients with tuberous sclerosis: concordance of interictal and ictal epileptiform activity.

OBJECTIVE: In the majority of patients with tuberous sclerosis complex (TSC) multifocal epileptiform activity is present interictally. Therefore, its value in identifying epilepsy surgery candidates has been doubted. We hypothesize that dominant interictal epileptiform foci are concordant with the ictal onset zone in TSC patients. METHODS: Consistency and dominance of focal interictal epileptiform activity was assessed in 19 patients with a clinical definite diagnosis of TSC. The ictal onset zone was identified. Concordance between interictal en ictal findings was analyzed. If concordance was found epilepsy surgery was proposed. RESULTS: We found dominant, consistently present, focal interictal epileptiform activity in 14 of the 19 patients. Concordance between the dominant interictal focus and the ictal onset zone was found in 11 of the 14 patients (79%). In one patient the ictal onset zone could not be identified and discordance was present in two patients. Epilepsy surgery was performed in six patients rendering three of them seizure free, and one had a seizure reduction >90%. In these patients local concordance was found whereas regional concordance was found in the two patients who did not benefit from epilepsy surgery. CONCLUSIONS: A dominant as well as a consistent interictal focus is concordant with the ictal onset zone in the majority of TSC patients. SIGNIFICANCE: Future studies of TSC patients addressing the value of interictal foci in the consideration of epilepsy surgery, in absence of clear ictal onset zone, are necessary.

Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial.

OBJECTIVES: The goals were to investigate how many subclinical seizures in full-term neonates with hypoxic-ischemic encephalopathy (HIE) would be missed without continuous amplitude-integrated electroencephalography (aEEG) and whether immediate treatment of both clinical and subclinical seizures would result in a reduction in the total duration of seizures and a decrease in brain injury, as seen on MRI scans. METHODS: In this multicenter, randomized, controlled trial, term infants with moderate to severe HIE and subclinical seizures were assigned randomly to either treatment of both clinical seizures and subclinical seizure patterns (group A) or blinding of the aEEG registration and treatment of clinical seizures only (group B). All recordings were reviewed with respect to the duration of seizure patterns and the use of antiepileptic drugs (AEDs). MRI scans were scored for the severity of brain injury. RESULTS: Nineteen infants in group A and 14 infants in group B were available for comparison. The median duration of seizure patterns in group A was 196 minutes, compared with 503 minutes in group B (not statistically significant). No significant differences in the number of AEDs were seen. Five infants in group B received AEDs when no seizure discharges were seen on aEEG traces. Six of 19 infants in group A and 7 of 14 infants in group B died during the neonatal period. A significant correlation between the duration of seizure patterns and the severity of brain injury in the blinded group, as well as in the whole group, was found. CONCLUSIONS: In this small group of infants with neonatal HIE and seizures, there was a trend for a reduction in seizure duration when clinical and subclinical seizures were treated. The severity of brain injury seen on MRI scans was associated with a longer duration of seizure patterns.

Additional value of two-channel amplitude integrated EEG recording in full-term infants with unilateral brain injury.

BACKGROUND: Amplitude integrated electroencephalography (aEEG) is a valuable tool for evaluating neonatal encephalopathy and identifying electrographic seizures. OBJECTIVE: To compare seizure activity and background pattern (BGP) between one-channel and two-channel aEEG recordings in full-term neonates. METHODS: The two-channel aEEG recordings (F3-P3; F4-P4) of 34 neonates with seizures were compared with single-channel recordings (P3-P4). RESULTS: All 34 infants with unilateral (n=14), diffuse (n=18) or without (n=2) brain injury had seizure patterns on one-channel and two-channel recordings, with 18% more seizure patterns detected with two-channel recording. In 79% of infants with unilateral injury more seizures were noted on the ipsilateral side compared to the contralateral side. In 39% of the infants with diffuse brain damage more seizures were found with two-channel recordings. A sensitivity of 65% was found when using the automatic seizure detection algorithm. In 4/14 (29%) infants with unilateral injury a more severely affected BGP was seen on the ipsilateral side compared to the BGP on one-channel recording. In infants with diffuse injury differences in BGP pattern were seen in 6-17% of the infants depending on the system used for scoring. CONCLUSION: Although there were no major differences found between seizure detection with one-channel or two-channel aEEG, in a subgroup of infants with a predominantly unilateral brain lesion, two-channel recording did provide additional information with identification of more seizure patterns on the affected side, sometimes also associated with a difference in BGP. To improve early diagnosis of unilateral lesions and improve seizure detection in these infants, routine use of two-channel recordings is recommended.

Detection of subclinical electroencephalographic seizure patterns with multichannel amplitude-integrated EEG in full-term neonates.

OBJECTIVE: To compare the seizure pattern detection rate of single-channel and multichannel amplitude-integrated EEG (aEEG), using conventional EEG (cEEG) as a gold standard, in full-term neonates with hypoxic-ischemic encephalopathy. The optimal electrode derivation for seizure detection with single-channel aEEG was also investigated. METHODS: Twelve infants with cEEG seizure patterns (10s) were investigated. cEEG signals were transformed into aEEG signals. Seizure patterns and the number of patients identified with 1 seizure patterns were calculated for single- and multichannel aEEG. RESULTS: On cEEG, 121 seizure patterns with a mean duration of 58s were identified, 68% of which occurred over the centrotemporal region. The sensitivity of aEEG for the detection of seizure patterns was 30% (C.I.: 0.22-0.38) for single-channel aEEG and 39% (C.I.: 0.31-0.48) for multichannel aEEG. Multichannel aEEG identified all patients with 1 seizure pattern (C.I.: 0.75-1.00), whereas single-channel aEEG (with C4-C3 as the optimal electrode derivation) identified all but one of the patients (C.I.: 0.66-0.99). CONCLUSIONS: Seizure pattern detection rate is slightly better with multichannel aEEG compared with single-channel (C4-C3) aEEG. Multichannel aEEG identified correctly all patients with 1 seizure pattern in this small selection of patients. SIGNIFICANCE: Single-channel aEEG may detect most patients (in a selected group) with severe neonatal seizures patterns; patient identification can be improved using multichannel recordings.

3T versus 1.5T phased-array MRI in the presurgical work-up of patients with partial epilepsy of uncertain focus.

PURPOSE: To study 3T compared to 1.5T phased array magnetic resonance imaging (MRI) in the presurgical work-up of patients with epilepsy with complex focus localization. MATERIALS AND METHODS: In all, 37 patients (>10 years) in preoperative work-up for epilepsy surgery were offered 3T in addition to 1.5T MRI if ambiguity existed about the epileptic focus. Scans were randomly reviewed by two observers, blinded for prior imaging, patient-identifying information, and each other's assessments, followed by a consensus meeting. The number of abnormal scans, detected lesions, and interobserver agreement were calculated and compared. The final consensus was compared to original scan reports. RESULTS: One observer identified 22 lesions in both 3 and 1.5T scans, while the second identified more lesions in 1.5T scans (28 vs. 20). 3T MRI had better interobserver agreement. 3T revealed more dysplasias, while 1.5T revealed more tissue loss and mesial temporal sclerosis (MTS). The final consensus yielded 29 lesions, whereas original reports identified only 17 lesions. CONCLUSION: The 3T scans revealed different lesions compared to 1.5T. Patients can benefit most from 3T scans when a dysplasia is suspected. Reevaluation by another experienced neuroradiologist is advised in case of negative or equivocal MRIs.

Prognosis after temporal lobe epilepsy surgery: the value of combining predictors.

PURPOSE: Although several independent predictors of seizure freedom after temporal lobe epilepsy surgery have been identified, their combined predictive value is largely unknown. Using a large database of operated patients, we assessed the combined predictive value of previously reported predictors included in a single multivariable model. METHODS: The database comprised a cohort of 484 patients who underwent temporal lobe surgery for drug-resistant epilepsy. Good outcome was defined as Engel class 1, one year after surgery. Previously reported independent predictors were tested in this cohort. To be included in our final prediction model, predictors had to show a multivariable p-value of <0.20. RESULTS: The final multivariable model included predictors obtained from the patient's history (absence of tonic-clonic seizures, absence of status epilepticus), magnetic resonance imaging [MRI; ipsilateral mesial temporal sclerosis (MTS), space occupying lesion], video electroencephalography (EEG; absence of ictal dystonic posturing, concordance between MRI and ictal EEG), and fluorodeoxyglucose positron emission tomography (FDG-PET; unilateral temporal abnormalities), that were related to seizure freedom in our data. The model showed an expected receiver-operating characteristic curve (ROC) area of 0.63 [95% confidence interval (CI) 0.57-0.68] for new patient populations. Intracranial monitoring and surgery-related parameters (including histology) were not important predictors of seizure freedom. Among patients with a high probability of seizure freedom, 85% were seizure-free one year after surgery; however, among patients with a high risk of not becoming seizure-free, still 40% were seizure-free one year after surgery. CONCLUSION: We could only moderately predict seizure freedom after temporal lobe epilepsy surgery. It is particularly difficult to predict who will not become seizure-free after surgery.

Detection of temporal lobe spikes: comparing nasopharyngeal, cheek and anterior temporal electrodes to simultaneous subdural recordings.

OBJECTIVE: To compare nasopharyngeal (NP), cheek and anterior temporal (AT) electrodes for the detection yield and localization of interictal spikes in temporal lobe epilepsy. METHODS: In patients evaluated for epilepsy surgery with subdural electrocorticography electrodes, we simultaneously recorded NP, cheek and AT electrodes. Two observers identified spikes in EEG traces and marked in which channels they occurred. Interobserver agreement was calculated using Cohen's kappa. For localization, data-sets with high interobserver agreement (kappa-value 0.4) were evaluated. The subdural distribution of NP and AT spikes was mapped. RESULTS: Seven patients were included, six were analyzed for localization. Only 1.5% of spikes recorded by cheek electrodes were not seen on temporal leads, while 25% of NP spikes were not seen on either. Spikes only recorded by NP electrodes had mesiobasal, while AT spikes had lateral temporal distribution. CONCLUSIONS: NP electrodes can increase EEG spike detection rate in temporal lobe epilepsy and are more useful than cheek electrodes. Spikes that are seen only on NP electrodes tend to be mesiobasal temporal lobe spikes. SIGNIFICANCE: Adding NP electrodes to scalp EEG can aid interictal spike detection and source localization, especially in short recordings like MEG-EEG.

Diagnosing cerebral collateral flow patterns: accuracy of non-invasive testing.

OBJECTIVE: With routine use of non-invasive methods to assess the internal carotid artery, it becomes increasingly important to clarify the diagnostic accuracy of transcranial Doppler (TCD) ultrasound and magnetic resonance angiography (MRA) compared with intra-arterial digital subtraction angiography (iaDSA) for the detection of collateral flow via the major intracerebral collateral branches. SUBJECTS AND METHODS: In a prospective study, we compared TCD via a temporal bone window and MRA (flow direction sensitive phase contrast and time of flight) examinations of the intracranial collateral flow with iaDSA in a cohort of 97 consecutive patients with recent transient or minor disabling cerebral ischaemia associated with an occlusion of the carotid artery (38 contralateral stenosis >70%). RESULTS: iaDSA allowed the evaluation of collateral flow via the anterior and posterior circle of Willis in 97 and 67 patients, respectively, TCD in 76 of 97 and 66 of 67 patients, MRA in 95 of 97 and 66 of 67 patients. MRA and TCD collateral flow measurements via the anterior part of the circle of Willis yielded a sensitivity of 83 and 82%, a specificity of 77 and 79% and a similar accuracy of 80%. MRA and TCD collateral flow measurements via the posterior communicating artery yielded a sensitivity of 33 and 76%, a specificity of 88 and 47% and an accuracy of 47 and 68%. CONCLUSION: As compared with iaDSA, combined MRA and TCD has a moderate to good diagnostic value for the examination of intracranial collateral flow in patients with symptomatic carotid occlusion.

The effect of intraduodenal glucose on muscle sympathetic nerve activity in healthy young and older subjects.

OBJECTIVE: The cardiovascular response to a meal is modulated by gastric distension and the interaction of nutrients, particularly carbohydrate, within the small intestine. We tested the hypothesis that the depressor effect of small intestinal glucose is greater in older than in young subjects, because the reflex increase in muscle sympathetic nerve activity (MSNA) is blunted by age. METHODS: The effects of intraduodenal glucose infusion (IDGI) on blood pressure, heart rate and MSNA were evaluated in eight healthy young subjects (4 women; mean age +/- SEM: 28.8 +/- 3.4 years), eight healthy elderly (4 women; 75.3 +/- 1.6 years) and in two patients with symptomatic postprandial hypotension (PPH), one young (21 years), and one old (90 years). RESULTS: In both young and elderly healthy subjects, IDGI decreased blood pressure (P < 0.05), but the fall in systolic blood pressure was greater in the older subjects (-17.0 +/- 4.1 vs. -6.5 +/- 1.6 mmHg, P < 0.03). MSNA increased similarly, after infusion in both young (9.0 +/- 3.4 bursts/min) and elderly (7.8 +/- 1.0 bursts/min) subjects. Baroreflex sensitivity for number of sympathetic bursts was attenuated in the elderly (P < 0.03). The increase in burst area in the young patient with PPH was attenuated (18 vs. 63% in the healthy young group). INTERPRETATION: The fall in BP induced by IDGI was greater in healthy elderly compared to healthy young subjects. The reason for this is unclear, as they have similar increases in MSNA.

Decision-making in temporal lobe epilepsy surgery: the contribution of basic non-invasive tests.

PURPOSE: We studied the extent to which the widely used diagnostic tests contribute to the decision whether or not to perform temporal lobe epilepsy (TLE) surgery in The Netherlands. METHODS: This nation-wide, retrospective study included 201 consecutive patients referred for TLE surgery screening. The individual and combined contribution of nine index tests to the consensus decision to perform surgery was investigated. The contribution of each test was quantified using multivariable logistic regression and ROC curves. RESULTS: Surgery was performed in 119 patients (59%). Patient history and routine EEG findings were hardly contributory to decision-making, whereas a convergence of MRI with long-term interictal and ictal EEG findings correctly identified the candidates considered eligible for surgery (25% of total). Videotaped seizure semiology contributed less to the results. The area under the ROC curve of the combination of basic tests was 0.75. Ineligibility was never accurately predicted with any test combination. CONCLUSIONS: In the Dutch presurgical work-up, when MRI and long-term EEG findings were concordant, a decision for TLE surgery could be reached without further ancillary tests. Videotaped seizure semiology contributed less than expected to the final clinical decision. In our study, basic test findings alone were insufficient to exclude patients from surgery.

Should we reconsider epilepsy surgery? The motivation of patients once rejected.

The pre-surgical work-up of patients with medically refractory epilepsy changes with the availability of new diagnostic procedures. New diagnostic investigations may also open up prospects for patients rejected in the past. A cohort of 71 Dutch patients rejected for epilepsy surgery 0.5-5 years earlier were approached to evaluate their willingness to undergo novel techniques. 64 (90%) responded to a questionnaire evaluating social and medical status, quality of life (QoL) and motivation to be reconsidered for epilepsy surgery. Four patients (6%) did not have seizures during the last 6 months. 56 patients (88%) were highly motivated to undergo new diagnostic procedures. Inability to localize the seizure focus had been the reason for rejection in 70% of these. We conclude that most patients once rejected for epilepsy surgery would like to benefit from novel techniques.

Electrocorticography discharge patterns in patients with a cavernous hemangioma and pharmacoresistent epilepsy.

OBJECT: Neurodevelopmental lesions (NDLs) such as glioneuronal tumors and cortical dysplasia produce characteristic electrocorticography (ECoG) discharge patterns. Because cavernomas, another congenital abnormality, are also associated with pharmacoresistant epilepsy, the authors wondered whether they exhibit discharge patterns similar to those occurring in NDLs. METHODS: Intraoperative ECoG recordings from 19 patients with cavernomas and 54 with NDLs were reviewed for continuous spikes, bursts, or recruiting discharges and to determine whether these patterns were spatially coincident with the lesion. Relative densities of microglia and the intensity of Fe3+ staining in surgical samples were evaluated. Seizure outcome was assessed 1 year after surgery. RESULTS: The mean ages at seizure onset and surgery were higher in patients in the cavernoma group than in the NDL group (22.5 and 36.4 years compared with 10.0 and 25.2 years, respectively). Neocortical discharge patterns occurred equally in patients with either cavernomas (53%) or NDLs (41%). In the mesiotemporal area coincident bursts occurred more often in patients with cavernomas than patients with NDLs (55% compared with 10%, respectively). Coincident continuous spiking was associated with a longer duration of epilepsy in patients with cavernomas (23.5 years compared with 11.4 years for those without coincident continuous spiking) and with a lower age at seizure onset in those with NDLs (4.1 years compared with 11.8 years for those without coincident continuous spiking). In the cavernoma group the absence of coincident bursts was associated with high microglia density. There were no associations between the intensity of Fe3+ staining and discharge patterns, although the discharge patterns were associated with a worse outcome in patients with NDLs. CONCLUSIONS: In patients with NDLs, continuous spiking patterns may be markers of a widespread epileptogenic zone due to an early insult to the developing brain; in patients with cavernomas, such patterns may indicate secondary epileptogenesis. Microglia may inhibit discharge patterns in patients with cavernomas.

Neurodevelopmental outcome in term infants with status epilepticus detected with amplitude-integrated electroencephalography.

OBJECTIVES: This study evaluated seizure, patient characteristics, and neurodevelopmental outcome of term newborns with amplitude-integrated electroencephalography-detected status epilepticus. METHODS: Fifty-six term infants with status epilepticus were identified during a 12.5-year period. The time of onset of status epilepticus, background pattern before and after status epilepticus, success of controlling status epilepticus with antiepileptic drugs, and neurodevelopmental outcome were studied. RESULTS: The incidence of status epilepticus in our population was 18%. Forty-two infants (75%) had a poor outcome and 14 were normal at follow-up. When all infants were studied as a single group, we found that not the duration, but the background pattern was correlated with neurodevelopmental outcome. In 50% of the infants with a poor outcome, the background pattern was abnormal before the status epilepticus and in 71% after the status epilepticus. Among infants with a good outcome, background pattern was normal in 14% before and 7% after the status epilepticus. In a subgroup of 48 infants with hypoxic-ischemic encephalopathy, there was a significant difference in background pattern, as well as in duration of the status epilepticus between infants with a poor outcome, compared with those with a good outcome. In 48% of the infants with a poor outcome, the background pattern was abnormal before, and in 75% after the status epilepticus, compared with 25% and 13%, respectively, for those with a good outcome. In 57% of the infants with a hemorrhage or perinatal arterial stroke, the status epilepticus was not controlled with antiepileptic drugs, compared with 21% in infants with hypoxic-ischemic encephalopathy (not significant). CONCLUSIONS: The background pattern at the onset of status epilepticus was the main predictor of neurodevelopmental outcome. The duration of the status epilepticus was only of predictive value in the infants with hypoxic-ischemic encephalopathy. No association was found between the ability to control status epilepticus and subsequent neurodevelopmental outcome.

The added value of [18F]-fluoro-D-deoxyglucose positron emission tomography in screening for temporal lobe epilepsy surgery.

PURPOSE: [18F]-Fluoro-d-deoxyglucose positron emission tomography (FDG-PET) is an expensive, invasive, and not widely available technique used in the presurgical evaluation of temporal lobe epilepsy. We assessed its added value to the decision-making process in relation to other commonly used tests. METHODS: In a retrospective study of a large series of consecutive patients referred to the national Dutch epilepsy surgery program between 1996 and 2002, the contribution of FDG-PET, magnetic resonance imaging (MRI), and video-electroencephalogram (video-EEG) monitoring findings, alone or in combination, to the decision whether to perform surgery was investigated. The impact of FDG-PET was quantified by comparing documented decisions concerning surgery before and after FDG-PET results. RESULTS: Of 469 included patients, 110 (23%) underwent FDG-PET. In 78 of these patients (71%), FDG-PET findings led clinicians to change the decision they had made based on MRI and video-EEG monitoring findings. In 17% of all referred patients, the decision regarding surgical candidacy was based on FDG-PET findings. FDG-PET was most useful when previous MRI results were normal (p < 0.0001) or did not show unilateral temporal abnormalities (p < 0.0001), or when ictal EEG results were not consistent with MRI findings (p < 0.0001) or videotaped seizure semiology (p = 0.027). The positive and negative predictive values for MRI and video-EEG monitoring, which ranged from 0.48 to 0.67, were improved to 0.62 to 0.86 in combination with FDG-PET. CONCLUSIONS: In patients referred for TLE surgery, FDG-PET findings can form the basis for deciding whether a patient is eligible for surgery, and especially when MRI or video-EEG monitoring are nonlocalizing.

EEG-fMRI in the preoperative work-up for epilepsy surgery.

Epilepsy surgery requires precise localization of the epileptic source. EEG-correlated functional MRI (EEG-fMRI) is a new technique showing the haemodynamic effects of interictal epileptiform activity. This study assesses its potential added value in the presurgical evaluation of patients with complex source localization. Adult surgical candidates considered ineligible because of an unclear focus and/or presumed multifocality on the basis of EEG underwent EEG-fMRI. Interictal epileptic discharges (IEDs) in the EEG during fMRI were identified by consensus between two observers. Topographically distinct IED sets were analysed separately. Only patients with significant, positive blood oxygen level-dependent (BOLD) responses that were topographically related to the EEG were re-evaluated for surgery. Forty-six IED sets from 29 patients were analysed. In eight patients, at least one BOLD response was significant, positive and topographically related to the IEDs. These patients were rejected for surgery because of an unclear focus (n = 3), presumed multifocality (n = 2) or a combination of both (n = 3). EEG-fMRI improved localization in four out of six unclear foci. In patients with presumed multifocality, EEG-fMRI advocated one of the foci in one patient and confirmed multifocality in four out of five patients. In four patients EEG-fMRI opened new prospects for surgery and in two of these patients intracranial EEG supported the EEG-fMRI results. In these complex cases, EEG-fMRI either improved source localization or corroborated a negative decision regarding surgical candidacy. It is thus a valuable tool in the presurgical evaluation of patients. Guidelines for the use of EEG-fMRI in clinical practice are proposed.