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.

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.

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.

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.

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.

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.

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.

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.

Transcranial Doppler ultrasonography to confirm brain death: a meta-analysis.

OBJECTIVE: Barbiturate therapy or hypothermia precludes proper diagnosis of brain death either clinically or by EEG. Specific intracranial flow patterns indicating cerebral circulatory arrest (CCA) can be visualized by transcranial Doppler ultrasonography (TCD). The aim of this study was to assess the validity of TCD in confirming brain death. DESIGN: Meta-analysis of studies assessing the validity of TCD in confirming brain death. METHODS: A systematic review of articles in English on the diagnosis brain death by TCD, published between 1980 and 2004, was performed. An oscillating or reverberating flow and systolic spikes were considered to be compatible with CCA. The quality of each study was assessed using standardized methodological criteria. The literature was searched for any article reporting a false-positive result. RESULTS: Two high-quality and eight low-quality studies were included. Meta-analysis of the two high-quality studies showed a sensitivity of 95% (95% CI 92-97%) and a specificity of 99% (95% CI 97-100%) to detect brain death. Meta-analysis of all ten studies showed a sensitivity of 89% and a specificity of 99%. In the literature we found two false-positive results; however, in both patients brain-stem function did show brain death shortly thereafter. CONCLUSIONS: CCA by TCD in the anterior and posterior circulation predicted fatal brain damage in all patients; therefore, TCD can be used to determine the appropriate moment for angiography. Further research is needed to demonstrate that CCA by TCD on repeated examination can also predict brain death in all patients.

Resective epilepsy surgery in childhood: the Dutch experience 1992-2002.

PURPOSE: We present the outcome of resective epilepsy surgery in 69 pediatric patients who participated in the Dutch Collaborative Epilepsy Surgery Program (DCESP) between 1992 and 2002 with special emphasis on long-term follow-up. METHODS: Sixty-nine children (aged 3 months to 17 years) operated on before 2003 were included in this study (34 temporal resections (49%), 17 extra-temporal resections (24%) and 19 hemispherectomies (27%)). Engel classification was used to assess seizure outcome annually. Cognitive outcome was assessed if possible. Two telephone surveys were carried out with an interval of 2(1/2) years to obtain data on seizure frequency, use of AEDs and on aspects op psychosocial development. Kaplan-Meier survival curves were constructed to assess recurrence of seizures after initial postsurgical seizure freedom, based on both telephone surveys. RESULTS: Seventy percent scored Engel 1, 18% Engel 2, 6% Engel 3 and 6% Engel 4 at the time of the first telephone survey (2(1/2) years later: 77% Engel 1, 8% Engel 2, 12% Engel 3 and 3% Engel 4). Temporal resections were associated with the best seizure outcome (Engel 1 74% and 82%). AEDs could be withdrawn successfully in 53% of patients at time of the last follow-up. No negative impact on cognition was found. The first long-term follow-up (mean 4.5 years after surgery) measurement showed recurrence of seizures after initial seizure freedom in 17%. At time of the second long-term follow-up measurement (mean 7.5 years after surgery) this percentage had increased to 21%. CONCLUSIONS: Our results support previous reports that surgery for intractable epilepsy in pediatric patients can be safely performed with satisfactory long-term results. Best results are attained in temporal resections.

QEEG changes during carotid clamping in carotid endarterectomy: spectral edge frequency parameters and relative band power parameters.

Intraoperative monitoring is needed to identify accurately those patients in need of a shunt during carotid endarterectomy. EEG can be used for this purpose, but there is no consensus on the variables to use. Using a database consisting of 149 EEGs recorded from patients during carotid endarterectomy under isoflurane (n=61) or propofol (n=88) anesthesia and who did or did not receive a shunt, the authors investigated which of 16 derivations (common reference, Cz) and 12 parameters (relative and absolute powers and spectral edge frequencies [SEFs]) singly or in combination could best distinguish between the shunt and the nonshunt groups for the two anesthesia regimens. Receiver operating characteristic curves were used to select derivation/parameter combinations for three types of trend computation: (1) values of relative powers and SEFs during clamping (C) only, (2) clamp minus preclamp (baseline) differences (C-B), and (3) C-B differences in absolute logarithmic power (DeltalogP). For both anesthesia regimens, C-B computation distinguished best between the shunt and nonshunt groups. For isoflurane anesthesia, SEF parameters were the best, and for propofol anesthesia the relative power parameters. Discriminant analysis, in which additional derivation/parameter combinations were added, increased the discriminative power of the DeltalogP computation but not of the C or C-B computations. For isoflurane anesthesia, SEF 90% was the best single parameter for distinguishing between patients who did and did not need a shunt and the four best derivations were F3-Cz, P4-Cz, C4-Cz, and F7-Cz. For the propofol anesthesia, the relative power (C or C-B computations) of the delta band was the best and the four best derivations were F8-Cz, T4-Cz, C4-Cz, and F4-Cz.

Postneonatal epilepsy following amplitude-integrated EEG-detected neonatal seizures.

To assess the incidence of postneonatal epilepsy in term infants treated with antiepileptic drugs for neonatal seizure discharges that were detected with amplitude-integrated electroencephalography (aEEG), 206 term infants were monitored using this modality. They received antiepileptic drugs for clinical as well as subclinical neonatal seizures. Follow-up data were analyzed for the development of postneonatal epilepsy and for their neurodevelopmental outcome, assessed at 3, 9, 18 months, and 3 and 5 years of age. A total of 169 (82%) neonates received two or more antiepileptic drugs. Overall mortality was 39% (n = 80). Forty-one of the 126 survivors (33%) were abnormal at follow-up, and 12 of them developed postneonatal epilepsy (9.4%). Eighty-four children survived after hypoxic-ischemic encephalopathy grade II (n = 92), and 6 (7%) developed postneonatal epilepsy. In this subgroup, no postneonatal epilepsy was observed if seizures were controlled within 48 hours after birth and when not more than two antiepileptic drugs were required. Twenty-four children survived after an intracranial hemorrhage (n = 28), and only 1 (4%) developed postneonatal epilepsy. Eleven children survived after perinatal arterial stroke (n = 13), and 2 (18%) developed postneonatal epilepsy. In conclusion, the incidence of postneonatal epilepsy after treatment of clinical and subclinical neonatal seizures detected with continuous amplitude-integrated electroencephalography was 9.4%; This figure is lower than previously reported in children who only received treatment for clinical seizures.

What is the current evidence on decision-making after referral for temporal lobe epilepsy surgery? A review of the literature.

OBJECTIVES: Many patients thought to have temporal lobe epilepsy, are evaluated for surgical treatment. Decision-making in epilepsy surgery is a multidisciplinary, phased process involving complex diagnostic tests. This study reviews the literature on the value of different tests to decide on whether to operate. METHODS: Articles were selected when based on the consensus decision whether to perform temporal lobe surgery, or on the consensus localization or lateralization of the epileptic focus. The articles were scrutinized for sources of bias as formulated in methodological guidelines for diagnostic studies (STARD). RESULTS: Most studies did not fulfill the criteria, largely because they addressed prognostic factors in operated patients only. Ten articles met our inclusion criteria. In most articles, a single test was studied; SPECT accounted for five papers. Unbiased comparison of the results was not possible. CONCLUSION: Surprisingly little research in epilepsy surgery has focused on the decision-making process as a whole. Future studies of the added value of consecutive tests are needed to avoid redundant testing, enable future cost-efficiency analyses, and provide guidelines for diagnostic strategies after referral for temporal lobe epilepsy surgery.

Cognitive impairment is related to cerebral lactate in patients with carotid artery occlusion and ipsilateral transient ischemic attacks.

BACKGROUND AND PURPOSE: Patients with carotid artery occlusion (CAO) and ipsilateral transient ischemic attack (TIA) can have lasting cognitive impairment, despite the recovery of focal neurological deficits. We sought to assess whether cognitive impairment in these patients is associated with hemodynamic compromise and/or impaired cerebral metabolism. METHODS: In 39 consecutive patients with a TIA associated with an angiographically proven occlusion of the carotid artery, we examined (1) cognitive functioning, (2) cerebrovascular reserve capacity of the middle cerebral artery ipsilateral to the CAO as measured by transcranial Doppler ultrasound, and (3) metabolic ratios as measured by 1H-MR spectroscopy in the centrum semiovale ipsilateral to the symptomatic CAO. Findings were compared with those in healthy control subjects. RESULTS: As a group, patients were cognitively impaired. Mean CO2 reactivity and the mean ratio of N-acetyl aspartate to creatine were decreased. In approximately one third of patients, lactate was present in noninfarcted regions. The presence of lactate proved to be a stronger correlate of cognitive impairment than MRI-detected lesions (beta=0.41 versus beta=0.15). Cognitive impairment did not correlate with CO2 reactivity or the ratio of N-acetyl aspartate to creatine. CONCLUSIONS: This exploratory study in patients with CAO and ipsilateral TIA showed that 1H-MR spectroscopy-detected lactate in noninfarcted regions is a better indicator of cognitive impairment than MRI-detected lesions. Cognitive impairment did not correlate with CO2 reactivity.

Association between impaired carbon dioxide reactivity and ischemic lesions in arterial border zone territories in patients with unilateral internal carotid artery occlusion.

CONTEXT: Ischemic lesions in patients with internal carotid artery (ICA) steno-occlusive disease can be categorized on the basis of their location and presumed cause: external border zone infarcts, internal border zone infarcts, cortical infarcts, lacunar infarcts, and periventricular lesions. OBJECTIVE: To evaluate the association between the prevalence and size of ischemic lesions and cerebral vasomotor reactivity in patients with unilateral occlusion of the ICA. DESIGN: Cross-sectional study. SETTING: Referral center. PATIENTS: Seventy consecutive patients were included in this study. All patients had a transient or minor disabling retinal or cerebral ischemia that was associated with unilateral occlusion of the ICA. Ischemic lesions on magnetic resonance imaging were identified on hard copies, and volume measurements were obtained by a magnetic resonance workstation. Vasomotor reactivity was assessed with transcranial Doppler ultrasonography with carbon dioxide challenge. MAIN OUTCOME MEASURES: Prevalence and size of ischemic lesions. RESULTS: In the hemisphere ipsilateral to the ICA occlusion, we found an increased prevalence of internal border zone infarcts (P =.01), external borders zone infarcts (P<.001), and territorial infarcts (P =.02) compared with the contralateral hemisphere. Hemispheres with a carbon dioxide reactivity less than or equal to 18% demonstrated a significant increase in prevalence (P =.007) and volume (P =.003) of internal border zone infarcts compared with hemispheres with a carbon dioxide reactivity greater than or equal to 19%. No association between carbon dioxide reactivity and any other type of ischemic lesion was found. CONCLUSION: In patients with an ICA occlusion, only internal border zone infarcts demonstrate a significant association with diminished cerebral hemodynamics.

Diffusion-weighted magnetic resonance imaging and identification of the epileptogenic tuber in patients with tuberous sclerosis.

BACKGROUND: Patients with tuberous sclerosis complex and drug-resistant epilepsy may be considered candidates for epilepsy surgery. This demands the unambiguous demonstration of the epileptogenicity of one of the tubers. OBJECTIVE: To test whether diffusion-weighted magnetic resonance imaging enables differentiation of epileptogenic tubers from inert ones. METHODS: In 4 patients with clear unifocal interictal spike activity, fluid-attenuated inversion recovery and diffusion-weighted magnetic resonance imaging were performed. Apparent diffusion coefficient maps were calculated in the identified epileptogenic tuber and compared withthose in nonepileptogenic tubers and regions of normal-appearing cortex. RESULTS: A significant increase in the apparent diffusion coefficient was found in the epileptogenic tubers. Furthermore, the apparent diffusion coefficient of the nonepileptogenic tubers was significantly higher than the trace apparent diffusion coefficient of regions of normal-appearing cortex. CONCLUSION: Diffusion-weighted magnetic resonance imaging may be of clinical importance for the identification of epileptogenic tubers in patients with tuberous sclerosis and intractable epilepsy.