Electrographic Seizure Patterns Research Articles

Differential electrographic seizure patterns in malformations of cortical development, early life brain injury, and later life brain injury

Structural epilepsy is a chronic neurologic condition that may be caused by in utero malformations of cortical development (MCD) or post-natal brain injuries resulting in encephalomalacia. We hypothesized that the timing of epileptogenic insult would lead to distinct electrographic seizure patterns. Specifically, we predicted that later life insults would lead to longer duration seizures with higher proportion of focal: focal to bilateral tonic-clonic (FBTC) seizures and low rates of bihemispheric onset seizures, as compared to early life insults. We performed a retrospective chart review of 70 adult patients – 33 with epilepsy secondary to brain injury (9 with injury occurring before 16 years and 24 with injury occurring at or after 16 years) with resultant encephalomalacia on MR imaging and 37 with epilepsy secondary to MCD – admitted to the University of Pittsburgh Epilepsy Monitoring Unit for presurgical evaluation. There were no significant differences in duration of epilepsy or number of trialed seizure medications between the groups. We examined scalp EEG data for all patients, as well as intracranial EEG data in a subset. We analyzed seizure duration, seizure frequency, and seizure type (focal, FBTC, and bihemispheric onset) in three cohorts: MCD patients, patients with brain injury occurring in early life (<16 years old), and patients with brain injury occurring in later life (≥16 years old). Patients with later life brain injury had significantly longer and less frequent seizures as compared to MCD cohorts. There were no differences between MCD and early life brain injury cohorts. Seizure duration findings were corroborated in a subset of patients who additionally underwent intracranial EEG monitoring. Additionally, later life brain injury patients had significantly different seizure types as compared to MCD cohorts, with high rates of FBTC and low rates of bihemispheric onset. Again, there was no significant differences in seizure type between early life brain injury and MCD cohorts. These novel findings indicate the relevance of timing of epileptogenic insult on the electrophysiological characteristics of structural epilepsies.

The Fingerprint of Scalp-EEG in Drug-Resistant Frontal Lobe Epilepsies.

Scalp-EEG incompletely covers the frontal lobe cortex. Underrepresentation of frontobasal or frontomesial structures, fast ictal spreading, and false lateralization impede scalp-EEG interpretation. Hence, we investigated the significance of scalp-EEG in the presurgical workup of frontal lobe epilepsy. Using descriptive statistical methods and Pearson chi-squared test for group comparisons, we retrospectively investigated postsurgical outcome, interictal epileptiform discharges (iiEDs), and electrographic seizure patterns on scalp-EEG in 81 consecutive patients undergoing resective epilepsy surgery within the margins of the frontal lobe. Postoperatively, patients with frontopolar iiEDs (n = 7) or concordant frontopolar iiED focus and seizure-onset (n = 2) were seizure free (n = 7/7, Engel Ia). MRI-positive patients with frontopolar iiEDs or frontopolar seizure-onset (n = 1/8 Engel Id, n = 7/8 Engel Ia) underwent surgery without stereo-EEG. Thirteen of 16 patients with frontolateral (n = 8/10, Engel Ia), or left frontobasal (n = 5/6, Engel Ia) seizure-onset undergoing further stereo-EEG, were seizure-free postoperatively. Seizure-onset prevalent over one electrode (n = 37/44 Engel I, p = 0.02), fast activity (FA)/flattening at seizure-onset (n = 29/33 Engel I, p = 0.02), FA/flattening during the seizure (n = 38/46 Engel I, p = 0.05), or focal rhythmic sharp-/spike-/polyspike-and-slow waves during the seizure (n = 24/31, Engel Ia, p = 0.05) were favorable prognostic markers. Interictal polyspike waves (p = 0.006 for Engel Ia) and interictal paroxysmal FA (p = 0.02 for Engel I) were unfavorable prognostic markers. Frontopolar scalp-EEG findings serve as biomarkers for predicting favorable surgical outcome in lesional frontal lobe epilepsy. Consequently, careful analysis of scalp-EEG assists in bypassing stereo-EEG in these patients.

Expert and deep learning model identification of iEEG seizures and seizure onset times.

Hundreds of 90-s iEEG records are typically captured from each NeuroPace RNS System patient between clinic visits. While these records provide invaluable information about the patient's electrographic seizure and interictal activity patterns, manually classifying them into electrographic seizure/non-seizure activity, and manually identifying the seizure onset channels and times is an extremely time-consuming process. A convolutional neural network based Electrographic Seizure Classifier (ESC) model was developed in an earlier study. In this study, the classification model is tested against iEEG annotations provided by three expert reviewers board certified in epilepsy. The three experts individually annotated 3,874 iEEG channels from 36, 29, and 35 patients with leads in the mesiotemporal (MTL), neocortical (NEO), and MTL + NEO regions, respectively. The ESC model's seizure/non-seizure classification scores agreed with the three reviewers at 88.7%, 89.6%, and 84.3% which was similar to how reviewers agreed with each other (92.9%-86.4%). On iEEG channels with all 3 experts in agreement (83.2%), the ESC model had an agreement score of 93.2%. Additionally, the ESC model's certainty scores reflected combined reviewer certainty scores. When 0, 1, 2 and 3 (out of 3) reviewers annotated iEEG channels as electrographic seizures, the ESC model's seizure certainty scores were in the range: [0.12-0.19], [0.32-0.42], [0.61-0.70], and [0.92-0.95] respectively. The ESC model was used as a starting-point model for training a second Seizure Onset Detection (SOD) model. For this task, seizure onset times were manually annotated on a relatively small number of iEEG channels (4,859 from 50 patients). Experiments showed that fine-tuning the ESC models with augmented data (30,768 iEEG channels) resulted in a better validation performance (on 20% of the manually annotated data) compared to training with only the original data (3.1s vs 4.4s median absolute error). Similarly, using the ESC model weights as the starting point for fine-tuning instead of other model weight initialization methods provided significant advantage in SOD model validation performance (3.1s vs 4.7s and 3.5s median absolute error). Finally, on iEEG channels where three expert annotations of seizure onset times were within 1.5 s, the SOD model's seizure onset time prediction was within 1.7 s of expert annotation.

Deep net detection and onset prediction of electrographic seizure patterns in responsive neurostimulation.

Managing the progress of drug-resistant epilepsy patients implanted with the Responsive Neurostimulation (RNS) System requires the manual evaluation of hundreds of hours of intracranial recordings. The generation of these large amounts of data and the scarcity of experts' time for evaluation necessitate the development of automatic tools to detect intracranial electroencephalographic (iEEG) seizure patterns (iESPs) with expert-level accuracy. We developed an intelligent system for identifying the presence and onset time of iESPs in iEEG recordings from the RNS device. An iEEG dataset from 24 patients (36 293 recordings) recorded by the RNS System was used for training and evaluating a neural network model (iESPnet). The model was trained to identify the probability of seizure onset at each sample point of the iEEG. The reliability of the net was assessed and compared to baseline methods, including detections made by the device. iESPnet performance was measured using balanced accuracy and the F1 score for iESP detection. The prediction time was assessed via both the error and the mean absolute error. The model was evaluated following a hold-one-out strategy, and then validated in a separate cohort of 26 patients from a different medical center. iESPnet detected the presence of an iESP with a mean accuracy value of 90% and an onset time prediction error of approximately 3.4 s. There was no relationship between electrode location and prediction outcome. Model outputs were well calibrated and unbiased by the RNS detections. Validation on a separate cohort further supported iESPnet applicability in real clinical scenarios. Importantly, RNS device detections were found to be less accurate and delayed in nonresponders; therefore, tools to improve the accuracy of seizure detection are critical for increasing therapeutic efficacy. iESPnet is a reliable and accurate tool with the potential to alleviate the time-consuming manual inspection of iESPs and facilitate the evaluation of therapeutic response in RNS-implanted patients.

Evidence for spreading seizure as a cause of theta-alpha activity electrographic pattern in stereo-EEG seizure recordings.

Intracranial electroencephalography is a standard tool in clinical evaluation of patients with focal epilepsy. Various early electrographic seizure patterns differing in frequency, amplitude, and waveform of the oscillations are observed. The pattern most common in the areas of seizure propagation is the so-called theta-alpha activity (TAA), whose defining features are oscillations in the θ − α range and gradually increasing amplitude. A deeper understanding of the mechanism underlying the generation of the TAA pattern is however lacking. In this work we evaluate the hypothesis that the TAA patterns are caused by seizures spreading across the cortex. To do so, we perform simulations of seizure dynamics on detailed patient-derived cortical surfaces using the spreading seizure model as well as reference models with one or two homogeneous sources. We then detect the occurrences of the TAA patterns both in the simulated stereo-electroencephalographic signals and in the signals of recorded epileptic seizures from a cohort of fifty patients, and we compare the features of the groups of detected TAA patterns to assess the plausibility of the different models. Our results show that spreading seizure hypothesis is qualitatively consistent with the evidence available in the seizure recordings, and it can explain the features of the detected TAA groups best among the examined models.

Deep Versus Lobar Intraparenchymal Hemorrhage: Seizures, Hyperexcitable Patterns, and Clinical Outcomes.

To compare electrographic seizures, hyperexcitable patterns, and clinical outcomes in lobar and deep intraparenchymal hemorrhage. Additionally, to characterize electrographic seizure and hyperexcitable pattern predictors in each group and determine seizure risk with thalamic involvement. Retrospective cohort study. Tertiary academic medical center. Consecutive adult patients with nontraumatic intraparenchymal hemorrhage undergoing continuous electroencephalography at our center between January 2013 and December 2016. Not applicable. Based on head CT closest to the initial continuous electroencephalography session, we classified intraparenchymal hemorrhage as isolated deep (no insular, subarachnoid, subdural extension) or lobar. Hyperexcitable patterns included the following: periodic discharges, spike-wave complexes, any rhythmic delta other than generalized. We used Fisher exact test for categorical and Mann-Whitney U test for continuous variables. Multivariable regression identified predictors of electrographic seizures, hyperexcitable patterns, and poor outcomes (score of 1-2 on Glasgow Outcome Scale) in lobar intraparenchymal hemorrhage. The cohort comprised of 128 patients, 88 lobar, and 40 deep intraparenchymal hemorrhage. Electrographic seizures occurred in 17% of lobar and 5% of deep intraparenchymal hemorrhage (p = 0.09). Hyperexcitable patterns were more frequent in the lobar group (44.3% vs 17.5%; p = 0.005). In multivariable analyses in the lobar group, lateralized rhythmic delta activity predicted electrographic seizures (odds ratio, 6.24; CI, 1.49-26.08; p = 0.012); insular involvement predicted hyperexcitable patterns (odds ratio, 4.88; CI, 1.36-17.57; p = 0.015); coma, temporal lobe involvement, intraparenchymal hemorrhage volume, and electrographic seizures predicted poor outcome. Thalamic involvement did not affect electrographic seizures or hyperexcitable patterns in either group. Electrographic seizures are frequent in lobar intraparenchymal hemorrhage, occurring in one in six monitored patients, as opposed to only 5% in isolated deep intraparenchymal hemorrhage not extending to cortex/insula, subarachnoid, or subdural spaces. Patients with lobar intraparenchymal hemorrhage and lateralized rhythmic delta activity were six times as likely to have electrographic seizures, which were associated with 5.47 higher odds of a poor outcome. Coma, temporal lobe involvement, hematoma volume, and electrographic seizures predicted poor outcome in lobar intraparenchymal hemorrhage.

Brain-responsive neurostimulation treatment in patients with GAD65 antibody-associated autoimmune mesial temporal lobe epilepsy.

Glutamic acid decarboxylase 65‐kilodalton isoform (GAD65) antibodies have been associated with multiple nonneurological and neurological syndromes including autoimmune epilepsy (AE). Although immunotherapy remains the cornerstone for the treatment of AE, those with GAD65 Ab‐associated AE (GAD65‐AE) remain refractory to immunotherapy and antiseizure medication (ASM). Outcomes of epilepsy surgery in this patient population have also been unsatisfactory. The role of neuromodulation therapy, particularly direct brain‐responsive neurostimulation therapy, has not been previously examined in GAD65‐AE. Here, we describe four consecutive patients with refractory GAD‐65‐associated temporal lobe epilepsy (GAD65‐TLE) receiving bilateral hippocampal RNS System treatment. The RNS System treatment was well tolerated and effective in this study cohort. Three patients had a >50% clinical seizure reduction, and one patient became clinically seizure‐free following resective surgery informed by the RNS System data with continued RNS System treatment. In all four of our patients, the long‐term ambulatory data provided by the RNS System allowed us to gain objective insights on electrographic seizure lateralization, patterns, and burden as well as guided immunotherapy and ASM optimization. Our results suggest the potential utility of the RNS System in the management of ASM intractable GAD65‐AE.

The Spectrum of Electrographic Seizure Patterns in the Critically Ill

The Spectrum of Electrographic Seizure Patterns in the Critically Ill

Association of Closed-Loop Brain Stimulation Neurophysiological Features With Seizure Control Among Patients With Focal Epilepsy

A bidirectional brain-computer interface that performs neurostimulation has been shown to improve seizure control in patients with refractory epilepsy, but the therapeutic mechanism is unknown. To investigate whether electrographic effects of responsive neurostimulation (RNS), identified in electrocorticographic (ECOG) recordings from the device, are associated with patient outcomes. Retrospective review of ECOG recordings and accompanying clinical meta-data from 11 consecutive patients with focal epilepsy who were implanted with a neurostimulation system between January 28, 2015, and June 6, 2017, with 22 to 112 weeks of follow-up. Recorded ECOG data were obtained from the manufacturer; additional system-generated meta-data, including recording and detection settings, were collected directly from the manufacturer's management system using an in-house, custom-built platform. Electrographic seizure patterns were identified in RNS recordings and evaluated in the time-frequency domain, which was locked to the onset of the seizure pattern. Patterns of electrophysiological modulation were identified and then classified according to their latency of onset in relation to triggered stimulation events. Seizure control after RNS implantation was assessed by 3 main variables: mean frequency of seizure occurrence, estimated mean severity of seizures, and mean duration of seizures. Overall seizure outcomes were evaluated by the extended Personal Impact of Epilepsy Scale questionnaires, a patient-reported outcome measure of 3 domains (seizure characteristics, medication adverse effects, and quality of life), with a range of possible scores from 0 to 300 in which lower scores indicate worse status, and the Engel scale, which comprises 4 classes (I-IV) in which lower numbers indicate greater improvement. Electrocorticographic data from 11 patients (8 female; mean [range] age, 35 [19-65] years; mean [range] duration of epilepsy, 19 [5-37] years) were analyzed. Two main categories of electrophysiological signatures of stimulation-induced modulation of the seizure network were discovered: direct and indirect effects. Direct effects included ictal inhibition and early frequency modulation but were not associated with improved clinical outcomes (odds ratio [OR], 0.67; 95% CI, 0.06-7.35; P > .99). Only indirect effects-those occurring remote from triggered stimulation-were associated with improved clinical outcomes (OR, infinity; 95% CI, -infinity to infinity; P = .02). These indirect effects included spontaneous ictal inhibition, frequency modulation, fragmentation, and ictal duration modulation. These findings suggest that RNS effectiveness may be explained by long-term, stimulation-induced modulation of seizure network activity rather than by direct effects on each detected seizure.

F92. Dense array EEG utilization in outpatient clinic: 788 Cases

Dense array EEG (dEEG) covers entire scalp surface by 128 or 256 leads, with shorter inter-electrode distance, making a better spatial resolution. It has been utilized only in selected cases for intractable seizure and a part of the presurgical evaluation. It is time-consuming to analyze EEG because of exceeding number of channels beyond the space of LCD monitor. There was no study that dEEG was applied for routine outpatient EEG evaluation. This result may be compared with routine outpatient EEG by 10–20 recording. We utilized dense array EEG system (dEEG) for patients visiting neurology clinic for mental status change in recent past 2 years. Electrodes were applied by the cap system. EEG was recorded using high-impedance DC amplification system by EGI (Eugene, OR, USA), 128 channels with a sampling frequency of 1000 Hz. We developed “double-banana” based convenient montage so that all relevant leads information can be seen by one monitor size without moving the EEG images up and down, that enabled us to review a large number of dEEG quickly. A recording sensitivity was 7 uV/mm, HFF 120 Hz, LFF 1.0 Hz. Recording duration was 30 min for all the patients. 788 dEEG recordings were accumulated in our outpatient clinic. Among them, diffuse background slowing was seen in 117 cases (14.8%), focal slowing in 197 (25%), interictal epileptiform discharges were seen in 285 (36.1%). Among the IID cases, 157 (55.1% of IID cases: 19.9% of total) were electrographic seizure pattern. Moreover, scalp permeating HFO (frequency 50–120 Hz) were seen in 46 (5.8%) Infra-slow delta (Defined as frequency <1 Hz) was seen in 39 (4.9%). 128 channel dEEG is sufficiently increased the special resolution and higher yield of inter-ictal abnormalities including IID and focal slowing. Moreover, it would increase the detecting yield of focal abnormalities, i.e., electrographic rhythmic pattern, Infra-slow delta activities, and scalp permeating HFO. Routine outpatient utilization of dEEG may potentially be more efficient in detection of abnormality than routine 10–20 system recording.

Early ictal and interictal patterns in FIRES: The sparks before the blaze.

Febrile infection-related epilepsy syndrome (FIRES) is a catastrophic epileptic encephalopathy described as explosive onset of super refractory status epilepticus (SRSE) in previously healthy children. We describe electroencephalography (EEG) abnormalities in the hyperacute phase of FIRES, with the aim of contributing to the diagnostic characterization of a syndrome otherwise lacking specific biomarkers. This is a retrospective single-center, case series of seven children with FIRES. Cases were identified from a Neurocritical Care database. Patient characteristics and clinical course were obtained from electronic medical records. Electroencephalography recordings were reviewed in two segments: the initial 12 h of recording and the 12 h prior to initiation of a medically induced burst suppression (BS). Fourteen 12-h segments of video-electroencephalography (EEG) recordings were analyzed for commonalities. A beta-delta complex resembling extreme delta brush (EDB) occurred in at least one 12-h segment for all patients. In six patients, seizures were brief and relatively infrequent during the first recording, with a gradual evolution to status epilepticus by the second. We observed a characteristic electrographic seizure pattern in six of seven patients with prolonged focal fast activity at onset. Shifting seizures were seen in four of seven patients. The diagnosis of FIRES is typically assigned late in a patient's clinical course, which has broad implications for clinical care and research. We retrospectively analyzed acute EEG features in seven patients with FIRES and discovered three common features: gradual increase in seizure burden, presence of a recurrent EDB, and a typical seizure pattern. Recognition of this pattern may facilitate early diagnosis and treatment.

Effectiveness of ketogenic diet in pentylenetetrazol-induced and kindling rats as well as its potential mechanisms

The effects and mechanisms of ketogenic diets (KD) are unclear. In this study, we aimed to reveal electrographic and behavioral thresholds in responses to the KD in pentylenetetrazol (PTZ)-induced seizures, as well as its antiepileptogenic effects on PTZ-kindling rats. Additionally, we investigated the potential link between KD and expression levels of two cation chloride co-transporters: K+–Cl− co-transporter 2 (KCC2) and Na+–K+–Cl− co-transporter 1 (NKCC1). The KD group had significantly higher electrographic thresholds than the control (ND) group for the first spike-and-wave, subcontinuous spike-and-wave, high amplitude spike-and-wave, and polyspikes both in the cortex and hippocampus. Compared to the ND group, the KD group had higher behavioral thresholds for behavioral absence, first jerk, first overt myoclonia, and generalized seizures. In the PTZ-kindling model, KD not only prolonged the latency of myoclonic and clonic convulsions, but shortened clonic and generalized duration. In addition, KD rats had higher KCC2 protein expression before kindling, during myoclonic jerks, and GTCS compared with ND rats. There were no significant differences in NKCC1 protein levels between both groups following the four-week dietary intervention without PTZ exposure (before kindling). Moreover, KD inhibited the upregulation of NKCC1 expression induced by kindling in myoclonic jerks and GTCS. Therefore, our findings demonstrated that KD had antiepileptic features in elevating thresholds to most electrographic and behavioral seizure patterns in PTZ-induced rats, as well as delaying the progression and alleviating the severity of seizure in PTZ-kindling model. The antiepileptogenic effects of KD may be attributed to its regulatory properties on KCC2 and NKCC1 protein expression.

Epilepsy in Prader–Willi syndrome: experience of a national referral centre

The aim of the study was to characterize epilepsy, febrile seizures, electrographic features, and brain abnormalities in a large, national cohort of individuals with Prader-Willi syndrome (PWS). This was an observational cohort study. Clinic charts of 126 individuals (63 males, 63 females) with genetically confirmed PWS (due to a deletion in 72 cases, to uniparental disomy [UPD] in 51 cases, and to an imprinting centre defect in two cases), aged from 1 month to 48 years (mean age 13y), were reviewed and 119 interviews conducted. Information regarding seizures, medication, imaging studies, and family history of seizures was collected. Ninety-five individuals (aged 1mo-48y) underwent electroencephalography (EEG). Five individuals had epilepsy (4.0%), three of whom had major cerebral findings on imaging, and eight others had febrile seizures (6.4%). Of the three genetic abnormalities, deletion was associated with seizures. Focal epileptiform abnormalities were found in 12 out of 94 individuals, and five out of these 12 had a frank electrographic seizure pattern. Epileptogenic EEG abnormalities were associated with young age. The risk of epilepsy and febrile seizures in PWS is significantly lower than in Angelman syndrome and is associated with brain abnormalities. Electrographic seizures and focal epileptiform activity were present in 5% of individuals and were associated with young age. The underpinnings of epileptiform abnormalities in PWS and how they differ from those of the Angelman syndrome should be studied further.

TRANSCRANIAL MAGNETIC STIMULATION (TMS) MODULATES EPILEPTIFORM DISCHARGES IN PATIENTS WITH FRONTAL LOBE EPILEPSY: A PRELIMINARY EEG-TMS STUDY

TMS is being increasingly used as a noninvasive brain stimulation technique for the therapeutic management of partial epilepsies. However, the acute effects of TMS on epileptiform discharges (EDs, i.e. interictal epileptiform activity and subclinical electrographic seizure patterns) remain unexplored. To investigate whether TMS can modulate EDs in partial epilepsy. In Experiment Set 1, the safety of the TMS protocol was investigated in 10 well-controlled by anti-epileptic drugs (AEDs) epileptic patients. In Experiment Set 2, the effects of TMS on EDs were studied in three subjects with intractable frontal lobe epilepsies, characterized by particularly frequent EDs. TMS was applied over the electrographic focus with a circular and a figure of eight coil while recording EEG with a 60-channel TMS-compatible EEG system. The effectiveness of TMS in aborting EDs was investigated using survival analysis and brain connectivity analysis. The TMS protocol was well-tolerated. TMS was an effective method to abort EDs even when adjusting for its latency with respect to ED onset (CMH test, p < 0.0001). While the effective brain connectivity around the epileptic focus increased significantly during EDs (p < 0.01), with TMS administration the increase was not statistically significant. TMS can modulate EDs in patients with epileptogenic foci in the cortical convexity and is associated with reversal of ED-induced changes in brain connectivity.

Atypical Presentation of Subclinical Rhythmic Electrographic Discharge of Adults (SREDA) in a Patient with Idiopathic Generalized Epilepsy

ABSTRACT.Subclinical rhythmic electrographic discharge of adults (SREDA) is considered a benign EEG pattern of uncertain significance, although it may closely resemble an electrographic seizure pattern. SREDA was first described by Westmoreland and Klass in 1981 as a distinctive rhythmic and rare EEG pattern primarily seen in older subjects. The typical pattern consists of sharp contoured, non-evolving 5 to 7 Hz theta rhythm with a widespread bilaterally synchronous distribution, but maximal over the parietal and posterior temporal regions. It usually lasts for a few seconds to several minutes without clinical association. Later in 1997, several unusual variants of SREDA were reported consisting of variations in frequency, morphology, topographic distribution, duration, and stage of alertness. We report SREDA in a patient with idiopathic generalized epilepsy which shows some atypical features (such as asynchronous onset, bifid waveforms, asymmetry, and fragmentation) and mimics a secondarily generalized partial seizure. It is important to successfully identify SREDA to avoid misdiagnosis and incorrect treatment. The technologist's contribution is essential and valuable. EEG technologists and interpreters should be aware of typical and atypical features of SREDA and its wide spectrum.

Do subclinical electrographic seizure patterns affect heart rate and its variability?

Autonomic symptoms during seizures may provide information on seizure onset zone. We investigated whether changes in heart rate (HR) and HR variability (HRV) occur during subclinical electrographic seizure patterns, and whether these have a localising/lateralising value. EEG and ECG recordings of pharmacoresistant epilepsy patients who underwent intracranial video-EEG telemetry were reviewed. Ultra-short-term HRV expressed as standard deviation of the mean before, during and after the subclinical seizure pattern was determined in 10s epochs. Statistics were done with a linear mixed regression model. Values are expressed as mean+/-SD. 26 patients (38+/-10 years, 13 of either gender) have been included; 7 patients with temporal lobe epilepsy (TLE) of either side as well as 7 (right-sided lesion) and 5 patients (left-sided lesion) with frontal lobe epilepsy (FLE). A total of 74 subclinical events (2-3 per patients) were analysed. Pooled data for HR only weakly increased during and after the subclinical pattern with a mean HR of 80+/-10 bpm before to 82+/-11 bpm during (p=0.03) and 81+/-10 bpm after subclinical patterns (p=0.06). HR was higher in patients with left TLE as compared to right TLE (p=0.001). In FLE patients only, the change in HR was correlated with the spatial extent of electrographic pattern localised (p=0.03). Mean HRV did not change during or after subclinical patterns. HRV was; however, lower in TLE patients with left-sided subclinical patterns as compared to right-sided patterns (pre-event HRV left 13+/-6 ms, right 34+/-16 ms). Our data revealed only minimal changes in autonomic cardiac function during highly localised electrographic seizure patterns and this had no localising/lateralising value.

FDG-PET and MRI in potassium channel antibody-associated non-paraneoplastic limbic encephalitis: correlation with clinical course and neuropsychology

We report a patient with potassium channel antibody-associated non-paraneoplastic limbic encephalitis (NPLE) in whom repeated fluorodeoxyglucose-positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) are correlated with epileptic activity and memory performance during the course of disease. A 32-year-old woman suffered from prolonged global amnesia after two generalized tonic-clonic seizures due to NPLE. Initially, MRI showed swelling of the left hippocampus. In FDG-PET, however, bitemporomesial hypermetabolism was seen corresponding to frequent bitemporal independent seizure patterns. Also neuropsychological impairments pointed to a bitemporal involvement at this early stage. In parallel with improved control of electrographic seizure patterns, improvement was seen in FDG-PET and in memory performance. During the whole course, MRI showed only left-sided abnormalities, which correlated with a permanent verbal memory impairment. FDG-PET was more sensitive in showing the initial bitemporal involvement and correlated well with EEG findings and neuropsychological impairment in the acute phase of disease. In contrast, structural MRI better reflected persistent neuropsychological deficits.

Spatio-temporal profile of DNA fragmentation and its relationship to patterns of epileptiform activity following focally evoked limbic seizures

The specific electrographic activity responsible for seizure-induced DNA damage remains little explored. We therefore examined the regional and temporal appearance of DNA fragmentation and cell death and its relationship to specific electrographic seizure patterns in a rat model of focally evoked limbic epilepsy. Animals received intra-amygdaloid injection of kainic acid (KA) to induce seizures for 45 min during continuous electroencephalographic (EEG) monitoring, after which diazepam (30 mg/kg) was administered. DNA polymerase I-mediated biotin-dATP nick translation (PANT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were used to detect single- and double-stranded DNA breaks, respectively. Injection of 0.01 μg KA induced seizures characterized by ictal fast activity but without consequent brain injury. By contrast, 0.1 μg KA induced an additional pattern of seizure activity characterized by bursts of high frequency polyspike paroxysmal discharges. In these animals, there was a significant reduction in numbers of pyramidal neurons within the ipsilateral and contralateral CA3 subfield of the hippocampus, detectable as little as 4 h following seizures. PANT- and TUNEL-positive cells appeared in similar numbers 16 h following seizure cessation within the CA3, declining after 72–96 h. Varying the duration of polyspike paroxysmal discharges determined that as little as 30 s elicited maximal injury. These data suggest single- and double-stranded DNA breaks are generated during the cell death process and are consequent on a specific component of seizure activity electrographically determined.

Characterization and comparison of local onset and remote propagated electrographic seizures recorded with intracranial electrodes.

To compared the ictal discharge patterns between local onset and remote propagated electrographic seizures recorded with chronic intracranial electrodes. The electrophysiological data from 88 consecutive patients who underwent chronic intracranial EEG monitoring were retrospectively reviewed. The early and late discharge patterns of electrographic seizures at local onset and distant propagated sites were determined by blinded visual inspection and computerized analysis. Four early and three late electrographic seizure patterns were observed at the local onset sites. The four early patterns consisted of a rhythmic discharge in the beta range ("beta buzz"), rhythmic alpha-theta activity, rhythmic sharp waves in the delta range, and an irregular spike discharge. The three distinct late-discharge patterns consisted of a late beta buzz, rhythmic sharp theta activity, and a rhythmic polyspike and wave discharge. At remote propagated sites, electrographic seizures could be divided into two different types according to their early discharge pattern. The first was unique to remote propagated electrographic seizures and consisted of a rhythmic theta-delta activity correlated with the concurrent activity at the local-onset site. The second remote initiation type consisted of patterns indistinguishable from the earlier discharge patterns recorded at the local onset site. The initial ictal discharge pattern recorded with intracranial electrodes can assist in differentiating local onset and remote propagated electrographic seizures, with rhythmic round theta-delta activity being unique to distant propagated sites. Nevertheless, the initial discharge of a subclass of remote propagated electrographic seizures consists of an independent pattern indistinguishable from that observed at local onset sites.

Motor expression of kainic acid seizures is attenuated by dopamine depletion in mice

We studied the effect of striatal dopamine depletion induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice on kainic acid (KA) evoked seizures. MPTP, 36 mg/kg i.p. for 3 days, caused an 80% drop of striatal dopamine. Animals pretreated with MPTP, plus controls treated with saline, were challenged with five different convulsant doses of KA (3, 6, 12, 18 and 36 mg/kg i.p.). The seizures were monitored by electrographic recording and behavioral observation. MPTP pretreatment greatly attenuated the severity of the convulsions and the mortality induced by KA. The effect was mostly evident at the intermediate and at the high doses of KA. Surprisingly, no differences between the MPTP and control groups were found on the intensity and time course of the electrical seizures. Increment doses of KA resulted in a more severe electrographic seizure pattern in both the saline and the MPTP pretreated groups. Our data suggest that the dopamine depletion induced by MPTP does not alter the genesis of KA induced seizures, but may alter the function of cerebral structures involved in the control of seizure motor expression.