The Single Word Auditory Comprehension (SWAC) test: A simple method to identify receptive language areas with electrical stimulation.

OBJECTIVES: Resective surgery for medically refractory epilepsy in proximity to speech receptive areas requires balancing adequate resection of the epileptogenic zone for optimal seizure control with preservation of function. We develop a simple test (Single Word Auditory Comprehension or SWAC) to localize speech receptive areas by evaluating patients' ability to comprehend a single word. METHODS: Patients were studied during presurgical or intraoperative assessment for epilepsy with intracranial electrodes. They were asked to listen to a common word (target word) and to describe what it meant without saying the target word. Electrical stimulation (trains of biphasic 2-ms pulses, 50 Hz for 3 s) was delivered while the patient listened to the target word, not while the patient explained the meaning of the word. In six patients, SWAC test was carried out during extraoperative chronic recordings, and in one patient in the operating theater under local anesthesia. RESULTS: Among the 7 patients where the test identified deficits, 6 underwent resection (4 temporal, 1 supramarginal, and 1 occipital). Two patients showed temporary minor speech deficits after resection. No patient showed permanent speech deficits after resection. CONCLUSION/SIGNIFICANCE: The SWAC test is reliable, simple and fast to implement, and suitable for intraoperating mapping. It could be used as a simple initial test to identify receptive language areas where more complex additional tests can be performed.

Mechanisms underlying different onset patterns of focal seizures.

Focal seizures are episodes of pathological brain activity that appear to arise from a localised area of the brain. The onset patterns of focal seizure activity have been studied intensively, and they have largely been distinguished into two types-low amplitude fast oscillations (LAF), or high amplitude spikes (HAS). Here we explore whether these two patterns arise from fundamentally different mechanisms. Here, we use a previously established computational model of neocortical tissue, and validate it as an adequate model using clinical recordings of focal seizures. We then reproduce the two onset patterns in their most defining properties and investigate the possible mechanisms underlying the different focal seizure onset patterns in the model. We show that the two patterns are associated with different mechanisms at the spatial scale of a single ECoG electrode. The LAF onset is initiated by independent patches of localised activity, which slowly invade the surrounding tissue and coalesce over time. In contrast, the HAS onset is a global, systemic transition to a coexisting seizure state triggered by a local event. We find that such a global transition is enabled by an increase in the excitability of the "healthy" surrounding tissue, which by itself does not generate seizures, but can support seizure activity when incited. In our simulations, the difference in surrounding tissue excitability also offers a simple explanation of the clinically reported difference in surgical outcomes. Finally, we demonstrate in the model how changes in tissue excitability could be elucidated, in principle, using active stimulation. Taken together, our modelling results suggest that the excitability of the tissue surrounding the seizure core may play a determining role in the seizure onset pattern, as well as in the surgical outcome.

Epilepsy in Qatar: Causes, treatment, and outcome.

OBJECTIVE: Qatar is a small country on the Eastern coast of the Arabian Peninsula. Its population is a unique mixture of native citizens and immigrants. We aimed to describe the features of epilepsy in Qatar as such information is virtually lacking from the current literature. METHODS: We summarized information retrospectively collected from 468 patients with epilepsy seen through the national health system adult neurology clinic. RESULTS: Epilepsy was classified as focal in 65.5% of the cases and generalized in 23%. Common causes of epilepsy were as follows: stroke (9%), hippocampal sclerosis (7%), infections (6%), and trauma (6%). Sixty-six percent of patients were receiving a single antiepileptic drug, with levetiracetam being the most frequently prescribed drug (41% of subjects). When the patients were divided by geographical background, remote infections caused the epilepsy in 15% of Asian patients (with neurocysticercosis accounting for 10%) but only in 1% of Qatari and 3% of Middle East/North African subjects (with no reported neurocysticercosis) (p<0.001). Cerebrovascular and neurodegenerative etiologies were the most prominent in Qataris, accounting for 14% (p=0.005) and 4% (p=0.03) of cases, respectively. The choice of antiepileptic drugs varied also according to the regional background, but the seizure freedom rate did not, averaging at 54% on the last clinic visit. SIGNIFICANCE: To our knowledge, this is the first detailed information about epilepsy in Qatar. The geographical origin of patients adds to the heterogeneity of this disorder. Neurocysticercosis should be in the etiological differential diagnosis of epilepsy in patients coming from Southeast Asian countries, despite the fact that it is not endemic to Qatar. The choice of antiepileptic drugs is influenced by the availability of individual agents in the patients' native countries but had no bearing on the final seizure outcome.

Single-cell recordings in the human medial temporal lobe.

Recordings from individual neurons in patients who are implanted with depth electrodes for clinical reasons have opened the possibility to narrow down the gap between neurophysiological studies in animals and non-invasive (e.g. functional magnetic resonance imaging, electroencephalogram, magnetoencephalography) investigations in humans. Here we provide a description of the main procedures for electrode implantation and recordings, the experimental paradigms used and the main steps for processing the data. We also present key characteristics of the so-called 'concept cells', neurons in the human medial temporal lobe with selective and invariant responses that represent the meaning of the stimulus, and discuss their proposed role in declarative memory. Finally, we present novel results dealing with the stability of the representation given by these neurons, by studying the effect of stimulus repetition in the strength of the responses. In particular, we show that, after an initial decay, the response strength reaches an asymptotic value after approximately 15 presentations that remains above baseline for the whole duration of the experiment.

Epilepsia partialis continua responsive to neocortical electrical stimulation.

Epilepsia partialis continua (EPC), defined as a syndrome of continuous focal jerking, is a rare form of focal status epilepticus that usually affects a distal limb, and when prolonged, can produce long-lasting deficits in limb function. Substantial electrophysiologic evidence links the origin of EPC to the motor cortex; thus surgical resection carries the risk of significant handicap. We present two patients with focal, drug-resistant EPC, who were admitted for intracranial video-electroencephalography monitoring to elucidate the location of the epileptogenic focus and identification of eloquent motor cortex with functional mapping. In both cases, the focus resided at or near eloquent motor cortex and therefore precluded resective surgery. Chronic cortical stimulation delivered through subdural strips at the seizure focus (continuous stimulation at 60-130 Hz, 2-3 mA) resulted in >90% reduction in seizures and abolition of the EPC after a follow-up of 22 months in both patients. Following permanent implantation of cortical stimulators, no adverse effects were noted. EPC restarted when intensity was reduced or batteries depleted. Battery replacement restored previous improvement. This two-case report opens up avenues for the treatment of this debilitating condition.

The value of Magnetoencephalography to guide electrode implantation in epilepsy.

To investigate if Magnetoencephalography (MEG) can add non-redundant information to guide implantation sites for intracranial recordings (IR). The contribution of MEG to intracranial recording planning was evaluated in 12 consecutive patients assessed pre-surgically with MEG followed by IR. Primary outcome measures were the identification of focal seizure onset in IR and favorable surgical outcome. Outcome measures were compared to those of 12 patients matched for implantation type in whom non-invasive pre-surgical assessment suggested clear hypotheses for implantation (non-MEG group). In the MEG group, non-invasive assessment without MEG was inconclusive, and MEG was then used to further help identify implantation sites. In all MEG patients, at least one virtual MEG electrode generated suitable hypotheses for the location of implantations. No differences in outcome measures were found between non-MEG and MEG groups. Although the MEG group included more complex patients, it showed similar percentage of successful implantations as the non-MEG group. This suggests that MEG can contribute to identify implantation sites where standard methods failed.

A review of signal processing and machine learning techniques for interictal epileptiform discharge detection.

Brain interictal epileptiform discharges (IEDs), as one of the hallmarks of epileptic brain, are transient events captured by electroencephalogram (EEG). IEDs are generated by seizure networks, and they occur between seizures (interictal periods). The development of a robust method for IED detection could be highly informative for clinical treatment procedures and epileptic patient management. Since 1972, different machine learning techniques, from template matching to deep learning, have been developed to automatically detect IEDs from scalp EEG (scEEG) and intracranial EEG (iEEG). While the scEEG signals suffer from low information details and high attenuation of IEDs due to the high skull electrical impedance, the iEEG signals recorded using implanted electrodes enjoy higher details and are more suitable for identifying the IEDs. In this review paper, we group IED detection techniques into six categories: (1) template matching, (2) feature representation (mimetic, time-frequency, and nonlinear features), (3) matrix decomposition, (4) tensor factorization, (5) neural networks, and (6) estimation of the iEEG from the concurrent scEEG followed by detection and classification. The methods are compared quantitatively (e.g., in terms of accuracy, sensitivity, and specificity), and their general advantages and limitations are described. Finally, current limitations and possible future research paths related to this field are mentioned.

Do Interictal Epileptiform Discharges and Brain Responses to Electrical Stimulation Come from the Same Location? An Advanced Source Localization Solution.

Identification of seizure sources in the brain is of paramount importance, particularly for drug-resistant epilepsy patients who may require surgical operation. Interictal epileptiform discharges (IEDs), which may or may not be frequent, are known to originate from seizure networks. Delayed responses (DRs) to brain electrical stimulation have been recently discovered. If DRs and IEDs come from the same location and the DRs can be accurately localized, there will be a significant step in identification of the seizure sources. The solution to this important question has been investigated in this paper. For this, we have exploited the morphology of these spike-type events, as well as the variability in their temporal locations, to develop new constraints for an adaptive Bayesian beamformer that outperforms the conventional and recently proposed beamformers even for identifying correlated sources. This beamformer is applied to an array (a.k.a mat) of cortical EEG electrodes. The developed approach has been tested on 300 data segments from five epileptic patients included in this study, which clinically represent a large population of candidates for surgical treatment. As the significant outcome of applying this beamformer, it is very likely (if not certain) that for an epileptic subject, the IEDs and DRs originate from the same location in the brain. This paves the way for a quick identification of the source(s) of seizure in the brain.

Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies.

PURPOSE: Deep brain stimulation (DBS) of the thalamus is an emerging surgical option for people with medically refractory epilepsy that is not suitable for resective surgery, or in whom surgery has failed. Our main aim was to evaluate the efficacy of bilateral centromedian thalamic nucleus (CMN) DBS for seizure control in generalized epilepsy and frontal lobe epilepsy with a two-center, single-blind, controlled trial. METHODS: Participants were adults with refractory generalized or frontal lobe epilepsy. Seizure diaries were kept by patients/carers prospectively from enrollment. The baseline preimplantation period was followed by a control period consisting of a blind stimulation-OFF phase of at least 3 months, a 3-month blind stimulation-ON phase, and a 6-month unblinded stimulation-ON phase. The control period was followed by an unblinded long-term extension phase with stimulation-ON in those patients in whom stimulation was thought to be effective. KEY FINDINGS: Eleven patients were recruited at King's College Hospital (London, United Kingdom United Kingdom) and at University Hospital La Princesa (Madrid, Spain). Among the five patients with frontal lobe epilepsy, only one patient had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, two patients with frontal lobe epilepsy had >50% improvement in seizure frequency. All six patients with generalized epilepsy had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, five of the six patients showed >50% improvement in the frequency of major seizures (one became seizure free, one had >99% improvement, and three had 60-95% reduction in seizure frequency). Among patients with generalized epilepsy, the DBS implantation itself appears to be effective, as two patients remained seizure free during 12 and 50 months with DBS OFF, and the remaining four had 50-91% improvement in the initial 3 months with DBS OFF. SIGNIFICANCE: DBS implantation and stimulation of the CMN appears to be a safe and efficacious treatment, particularly in patients with refractory generalized epilepsy. CMN stimulation was not as effective in frontal lobe epilepsy, which requires further studies. DBS of the CMN should be considered as a treatment option, particularly in patients with refractory generalized epilepsy syndromes.

Neuromodulation Techniques in Children with Super-Refractory Status Epilepticus.

Status epilepticus (SE) is a life-threatening condition and medical emergency which can have lifelong consequences, including neuronal death and alteration of neuronal networks, resulting in long-term neurologic and cognitive deficits in children. When standard pharmacological treatment for SE is not successful in controlling seizures, the condition evolves to refractory SE (rSE) and finally to super-refractory SE (srSE) if it exceeds 24 h despite using anaesthetics. In this systematic review, we present literature data on the potential uses of clinical neuromodulation techniques for the management of srSE in children, including electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation. The evaluation of these techniques is limited by the small number of published paediatric cases (n = 25, one with two techniques) in peer-reviewed articles (n = 18). Although neuromodulation strategies have not been tested through randomised, prospective controlled clinical trials, this review presents the existing data and the potential benefits of neuromodulation therapy, suggesting that these techniques, when available, could be considered at earlier stages within the course of srSE intending to prevent long-term neurologic complications. Clinical trials aiming to establish whether early intervention can prevent long-term sequelae are necessary in order to establish the potential clinical value of neuromodulation techniques for the treatment of srSE in children.

Separating Inhibitory and Excitatory Responses of Epileptic Brain to Single-Pulse Electrical Stimulation.

To enable an accurate recognition of neuronal excitability in an epileptic brain for modeling or localization of epileptic zone, here the brain response to single-pulse electrical stimulation (SPES) has been decomposed into its constituent components using adaptive singular spectrum analysis (SSA). Given the response at neuronal level, these components are expected to be the inhibitory and excitatory components. The prime objective is to thoroughly investigate the nature of delayed responses (elicited between 100[Formula: see text]ms-1 s after SPES) for localization of the epileptic zone. SSA is a powerful subspace signal analysis method for separation of single channel signals into their constituent uncorrelated components. The consistency in the results for both early and delayed brain responses verifies the usability of the approach.

Localization of Epileptic Brain Responses to Single-Pulse Electrical Stimulation by Developing an Adaptive Iterative Linearly Constrained Minimum Variance Beamformer.

Delayed responses (DRs) to single pulse electrical stimulation (SPES) in patients with severe refractory epilepsy, from their intracranial recordings, can help to identify regions associated with epileptogenicity. Automatic DR localization is a large step in speeding up the identification of epileptogenic focus. Here, for the first time, an adaptive iterative linearly constrained minimum variance beamformer (AI-LCMV) is developed and employed to localize the DR sources from intracranial electroencephalogram (EEG) recorded using subdural electrodes. The prime objective here is to accurately localize the regions for the corresponding DRs using an adaptive localization method that exploits the morphology of DRs as the desired sources. The traditional closed-form linearly constrained minimum variance (CF-LCMV) solution is meant for tracking the sources with dominating power. Here, by incorporating the morphology of DRs, as a constraint, to an iterative linearly constrained minimum variance (LCMV) solution, the array of subdural electrodes is used to localize the low-power DRs, some not even visible in any of the electrode signals. The results from the cases included in this study also indicate more distinctive locations compared to those achievable by conventional beamformers. Most importantly, the proposed AI-LCMV is able to localize the DRs invisible over other electrodes.

EEG frequency during spike-wave discharges may predict treatment outcome in patients with idiopathic generalized epilepsies.

We report findings concerning the relationship between electroencephalography (EEG) frequency during spike-and-wave discharges (SWDs) and response to treatment in 21 patients with idiopathic generalized epilepsy (IGE). We studied patients whose EEG contained SWDs lasting at least 4 s. Among these patients, two groups could be distinguished on the basis of a subtle difference in EEG frequency during the first 2 s of the burst. The two groups differed markedly in their clinical response to medication, with the group becoming seizure-free during the next 1-2 years showing a spike-wave onset frequency of > 3.2 Hz, and those not seizure-free < 3.2 Hz (p = 0.0034, sensitivity 75% and specificity 92%). Given this strong effect in a relatively small group, further work is needed to clarify the predictive value of this frequency measure for clinical outcomes in absence epilepsies.

Cingulate epileptogenesis in hypothalamic hamartoma.

Hypothalamic hamartoma (HH) is a relatively rare cause of epilepsy, mainly affecting children. Nearly all patients develop gelastic seizures, often followed by other focal seizure types. Our case illustrates the mechanisms of epileptogenesis in HH. The patient developed gelastic attacks as a baby, and secondarily generalized seizures and drop attacks at 9 years of age. Magnetic resonance imaging (MRI) confirmed the presence of a HH. Presurgical assessment with intracranial electroencephalography (EEG) monitoring recorded gelastic seizures with generalized epileptiform activity. Functional stimulation of the hamartoma provoked gelastic attacks. Single pulse electrical stimulation (SPES) was used to identify epileptogenic cortex. SPES of the left cingular cortex provoked generalized responses similar to the spontaneous generalized discharges. Our results suggest that long-standing history of epilepsy in patients with HH may be related to additional sources of epileptogenic activity. Electrical stimulation performed in this patient provided additional data to favor the hypothesis of secondarily epileptogenesis in the cingulate gyrus independently from the primary origin in the HH.

[Colorectal cancer screening at Clínica Alemana, Santiago de Chile]. / Plan de tamizaje de cáncer colorrectal ("Mes del Colon") en la Clínica Alemana de Santiago de Chile.

INTRODUCTION: Colorectal cancer (CRC) incidence is rapidly increasing. It has been demonstrated that it can be prevented and cured when the diagnosis is made in early stages. OBJECTIVE: For this reason it is necessary to apply a screening program in asymptomatic patients. METHOD: Since 2003, we conducted a CRC screening plan called "Mes del Colon" at Clínica Alemana Santiago. A press and local diffusion campaign was designed. Open to the community CRC talks were scheduled. An ad hoc database was designed. An informed consent was available. Patients older than 50 years and high risk patients were included. Total colonoscopy and a medical interview after the procedure were included in the plan with favorable economic conditions. RESULTS: Since 2003, 1158 patients were included The 1.8% of them were excluded because of incomplete data or because they did not meet the inclusion criteria. The 54% of patients were women. Mean age was 58.4 years old and mean body mass index 25.5 kg/m2. Polipoid lesions were seen in 45% of the patients. Six (1%) of them were adenocarcinomas, 291 (57%) adenomas (98% tubular adenomas), 189 (37%) hyperplastic polyps and 25 (5%) miscellaneous lesions. In this series, the necessary number to investigate for 1 adenoma was 3.9. CONCLUSIONS: CRC prevention campaigns are needed due to the continuous increase of the incidence in our country. The detection of precursor or early lesions that are longstanding before becoming advanced cancer allows its treatment avoiding progression.

Incorporating Uncertainty in Data Labeling into Automatic Detection of Interictal Epileptiform Discharges from Concurrent Scalp-EEG via Multi-way Analysis.

Interictal epileptiform discharges (IEDs) are elicited from an epileptic brain, whereas they can also be due to other neurological abnormalities. The diversity in their morphologies, their strengths, and their sources within the brain cause a great deal of uncertainty in their labeling by clinicians. The aim of this study is therefore to exploit and incorporate this uncertainty (the probability of the waveform being an IED) in the IED detection system which combines spatial component analysis (SCA) with the IED probabilities referred to as SCA-IEDP-based method. For comparison, we also propose and study SCA-based method in which probability of the waveform being an IED is ignored. The proposed models are employed to detect IEDs in two different classification approaches: (1) subject-dependent and (2) subject-independent classification approaches. The proposed methods are compared with two other state-of-the-art methods namely, time-frequency features and tensor factorization methods. The proposed SCA-IEDP model has achieved superior performance in comparison with the traditional SCA and other competing methods. It achieved 79.9% and 63.4% accuracy values in subject-dependent and subject-independent classification approaches, respectively. This shows that considering the IED probabilities in designing an IED detection system can boost its performance.

Higher-order tensor decomposition based scalp-to-intracranial EEG projection for detection of interictal epileptiform discharges.

Objective.Interictal epileptiform discharges (IEDs) occur between two seizures onsets. IEDs are mainly captured by intracranial recordings and are often invisible over the scalp. This study proposes a model based on tensor factorization to map the time-frequency (TF) features of scalp EEG (sEEG) to the TF features of intracranial EEG (iEEG) in order to detect IEDs from over the scalp with high sensitivity.Approach.Continuous wavelet transform is employed to extract the TF features. Time, frequency, and channel modes of IED segments from iEEG recordings are concatenated into a four-way tensor. Tucker and CANDECOMP/PARAFAC decomposition techniques are employed to decompose the tensor into temporal, spectral, spatial, and segmental factors. Finally, TF features of both IED and non-IED segments from scalp recordings are projected onto the temporal components for classification.Main results.The model performance is obtained in two different approaches: within- and between-subject classification approaches. Our proposed method is compared with four other methods, namely a tensor-based spatial component analysis method, TF-based method, linear regression mapping model, and asymmetric-symmetric autoencoder mapping model followed by convolutional neural networks. Our proposed method outperforms all these methods in both within- and between-subject classification approaches by respectively achieving 84.2% and 72.6% accuracy values.Significance.The findings show that mapping sEEG to iEEG improves the performance of the scalp-based IED detection model. Furthermore, the tensor-based mapping model outperforms the autoencoder- and regression-based mapping models.

24-Hour video EEG in the evaluation of the first unprovoked seizure.

OBJECTIVE: To assess the gain in detection of epileptiform abnormalities in 24-hour EEG recordings following the first seizure. METHODS: We identified patients who underwent 24-hour video EEG (VEEG) with "first seizure" as an indication. We noted the presence or absence of epileptiform discharges (EDs) in the VEEG study and the latency for the appearance of such discharges. We compared the rate of EDs during the initial 60 min with those occurring only later during the recording. RESULTS: Data from 25 patients, aged 15 to 59, were included. Of the 11 patients with EDs, eight (73%) appeared only after 60 min of recording. This equates to a 32% absolute increase in the detection of EDs across all patients. The latency to first EDs varied from one to 1080 min with a median of 170 min. In four cases, actual subtle seizures were recorded. CONCLUSION: This study suggests an increase in the detection of EDs with the 24-hour studies compared to the traditional shorter recordings, in the context of a first seizure. SIGNIFICANCE: A standard EEG can be performed close to the seizure, followed by a longer up to 24-hour recording if the initial shorter study is unrevealing.

Focal reading epilepsy--a rare variant of reading epilepsy: a case report.

Reading epilepsy is a distinct form of epilepsy in which all or almost all seizures are precipitated by reading. Seizures typically show orofacial or jaw myoclonus. Nevertheless, reading epilepsy is not homogenous and its classification is unclear. We report a patient with reading-induced prolonged left temporal seizures, presenting clinically as dyslexia.

A method for detecting false bifurcations in dynamical systems: application to neural-field models.

In this article, we present a method for tracking changes in curvature of limit cycle solutions that arise due to inflection points. In keeping with previous literature, we term these changes false bifurcations, as they appear to be bifurcations when considering a Poincaré section that is tangent to the solution, but in actual fact the deformation of the solution occurs smoothly as a parameter is varied. These types of solutions arise commonly in electroencephalogram models of absence seizures and correspond to the formation of spikes in these models. Tracking these transitions in parameter space allows regions to be defined corresponding to different types of spike and wave dynamics, that may be of use in clinical neuroscience as a means to classify different subtypes of the more general syndrome.