Probability Of Seizures Research Articles

Prevalence of Tramadol Consumption in First Seizure Patients; a One-Year Cross-sectional Study.

Previous studies have shown that there is a probability of seizure even with therapeutic doses of tramadol. Yet, no accurate data exist regarding this problem in Iran. Therefore, the present study aimed to evaluate the prevalence of tramadol consumption in patients with first seizure referred to the emergency department (ED). In the present retrospective one-year cross-sectional study, all patients who were referred to the ED of Poursina Hospital, Rasht, Iran, with the complaint of first seizure were evaluated. Demographic data and data regarding history of tramadol consumption, duration, total dose, last dose, and time passed from the last dose of consumption were recorded and analyzed regarding the study questions using SPSS 20. 383 (68.9%) out of the 556 patients referred to the ED, were experiencing their first seizure (mean age 26.43 ± 6.48 years; 70.5% male). 84 (21.9%) patients had recently used tramadol. History of seizure in the family of tramadol consumers was significantly lower (3.6% compared to 11%; p = 0.036). Mean total tramadol consumption dose in the last 24 hours was 140.17 ± 73.53 mg (range: 50-300 mg). Duration of tramadol consumption was less than 10 days in 84.5% (df: 2; χ(2) = 96.1; p < 0.001). In addition, 62 (73.8%) patients had seizure within 6 hours of consumption (df: 3; χ(2) = 29.5; p < 0.001). Results of the present study showed that 21.9% of the patients with first seizure had a history of tramadol consumption. Seizure following tramadol consumption is more prevalent in the initial 10 days and within 6 hours of consumption. In addition, it seems that lower doses of tramadol may also induce seizure.

Specific features of epilepsy in children with brain tumors

Objective : to study the specific features of epilepsy in children and adolescents with brain tumors and to define the optimal tactics of management and antiepileptic therapy after surgical treatment. Patients and methods . Sixty-one patients aged 5 months to 15 years were examined. All the patients were diagnosed as having a brain tumor found in the presence of symptomatic epilepsy. They were all followed up for 5 years postsurgery or during their lifetime (in case of death). Comprehensive examination encompassing the assessment of history data and concomitant complaints, brain magnetic resonance imaging, video-EEC monitoring, and the neurological status (the presence of cognitive impairments and eye ground changes) was done in all the cases. The probability of epileptic seizures in the clinical presentation of the disease, their semiology, and frequency were studied. Results and discussion. Epileptic seizures were the major complaint in all the patients at the first visit to their doctor. The disease occurred with status epilepticus in 9% of the patients. Different types of generalized seizures were more common (53%; p≥0.05). The tumor was located above the tentorium of the cerebellum in most examinees (77%) and beneath it in the others (23%; p≤0.05). The significant clinical sign of a brain tumor in the epileptic children is focal neurological symptoms (72% of the cases). MRI was performed in children who had no focal neurological symptoms in the late periods. There was cerebrospinal fluid hypertension in 51% of the patients (p≥0.05) and cognitive impairments in 33% (p&lt;0.05). The maximum number (74%) of children with psycho-speech disorders and cognitive impairments were registered in the age group of 7–15 years. Eye ground changes characteristic of intracranial hypertension were identified in 19 epileptic children; they occurred in 27 patients more than 1 year after the onset of seizures. The late (few months-to-14 years) diagnosis of a brain tumor was stated in children with epileptic seizures. The diagnosis was established in patients with a tumor in the cerebral hemispheres in the later periods. The leading symptom in these children was epileptic seizures and EEG changes. The changes detectable by video-EEG monitoring with sleep inclusion were shown to be of diagnostic value.

Antiepileptic drug nonadherence predicts pediatric epilepsy seizure outcomes.

The aim of the study was to determine sociodemographic, biological epilepsy-specific, and adherence predictors of long-term pediatric seizure outcomes. This study is a prospective, longitudinal, observational study of antiepileptic drug (AED) adherence and seizure outcomes in children with newly diagnosed epilepsy. Patients were recruited from April 2006 to March 2009 and followed for 2 years. Objective, electronic monitors were used to assess AED adherence. Medical chart reviews assessed medical variables and seizure outcomes. Participants (n = 109) were 7.3 ± 2.9 years of age, and 62% male. Four adherence trajectory groups were identified: severe early nonadherence (n = 10), variable nonadherence (n = 16), moderate nonadherence (n = 40), and high adherence (n = 43). Two seizure probability trajectory groups were identified: high seizure (n = 28) and low seizure probability (n = 81). Participants with recognizable syndromes were less likely to be a member of the high seizure probability group (b = -2.372; odds ratio [OR] = 0.093; 95% confidence interval [CI]OR = 0.015, 0.595); those with the presence of epileptiform discharges on EEG were more likely to be in the high seizure probability group (b = 1.649; OR = 5.203; 95% CIOR = 1.422, 19.037). Adherence trajectory group status was a significant predictor of seizure trajectory group status (partial max-rescaled R(2) = 0.13). Adherence trajectories and 2 biological epilepsy-specific variables explain a similar proportion of the variability in longitudinal seizure outcomes. The relationship between AED nonadherence and seizure outcomes is not linear. Early adherence interventions could change the course of seizure outcomes, particularly if variability in adherence was minimized postdiagnosis.

The probability of seizures during EEG monitoring in critically ill adults

ObjectiveTo characterize the risk for seizures over time in relation to EEG findings in hospitalized adults undergoing continuous EEG monitoring (cEEG). MethodsRetrospective analysis of cEEG data and medical records from 625 consecutive adult inpatients monitored at a tertiary medical center. Using survival analysis methods, we estimated the time-dependent probability that a seizure will occur within the next 72-h, if no seizure has occurred yet, as a function of EEG abnormalities detected so far. ResultsSeizures occurred in 27% (168/625). The first seizure occurred early (<30min of monitoring) in 58% (98/168). In 527 patients without early seizures, 159 (30%) had early epileptiform abnormalities, versus 368 (70%) without. Seizures were eventually detected in 25% of patients with early epileptiform discharges, versus 8% without early discharges. The 72-h risk of seizures declined below 5% if no epileptiform abnormalities were present in the first two hours, whereas 16h of monitoring were required when epileptiform discharges were present. 20% (74/388) of patients without early epileptiform abnormalities later developed them; 23% (17/74) of these ultimately had seizures. Only 4% (12/294) experienced a seizure without preceding epileptiform abnormalities. ConclusionsSeizure risk in acute neurological illness decays rapidly, at a rate dependent on abnormalities detected early during monitoring. This study demonstrates that substantial risk stratification is possible based on early EEG abnormalities. SignificanceThese findings have implications for patient-specific determination of the required duration of cEEG monitoring in hospitalized patients.

THE FRICTION MECHANISM BETWEEN SURFACES WITH REGULAR MICRO GROOVES UNDER BOUNDARY LUBRICATION

The results of research related to the influence of partially regular microrelief parameters on the adhesion component of the friction factor under boundary lubrication are presented. It has been shown that micro grooves are effective under boundary friction on precision surfaces with low roughness when lack of film and probability of seizure appear. The deformation component of the friction force of surfaces with micro grooves has been studied. The time of micro running-in was the key factor while assessing the dependence of the deformation component on friction when taking into account the depth of micro grooves and their relative area. The research was conducted using a tribometer according to the friction model entitled “shaft &amp; flexible steel tape”.

Seizures after single-agent overdose with pharmaceutical drugs: Analysis of cases reported to a poison center

Context. Seizures during intoxications with pharmaceuticals are a well-known complication. However, only a few studies report on drugs commonly involved and calculate the seizure potential of these drugs. Objectives. To identify the pharmaceutical drugs most commonly associated with seizures after single-agent overdose, the seizure potential of these pharmaceuticals, the age-distribution of the cases with seizures and the ingested doses. Methods. A retrospective review of acute single-agent exposures to pharmaceuticals reported to the Swiss Toxicological Information Centre (STIC) between January 1997 and December 2010 was conducted. Exposures which resulted in at least one seizure were identified. The seizure potential of a pharmaceutical was calculated by dividing the number of cases with seizures by the number of all cases recorded with that pharmaceutical. Data were analyzed using descriptive statistics. Results. We identified 15,441 single-agent exposures. Seizures occurred in 313 cases. The most prevalent pharmaceuticals were mefenamic acid (51 of the 313 cases), citalopram (34), trimipramine (27), venlafaxine (23), tramadol (15), diphenhydramine (14), amitriptyline (12), carbamazepine (11), maprotiline (10), and quetiapine (10). Antidepressants were involved in 136 cases. Drugs with a high seizure potential were bupropion (31.6%, seizures in 6 of 19 cases, 95% CI: 15.4–50.0%), maprotiline (17.5%, 10/57, 95% CI: 9.8–29.4%), venlafaxine (13.7%, 23/168, 95% CI: 9.3–19.7%), citalopram (13.1%, 34/259, 95% CI: 9.5–17.8%), and mefenamic acid (10.9%, 51/470, 95% CI: 8.4–14.0%). In adolescents (15–19y/o) 23.9% (95% CI: 17.6–31.7%) of the cases involving mefenamic acid resulted in seizures, but only 5.7% (95% CI: 3.3–9.7%) in adults (≥ 20y/o; p < 0.001). For citalopram these numbers were 22.0% (95% CI: 12.8–35.2%) and 10.9% (95% CI: 7.1–16.4%), respectively (p = 0.058). The probability of seizures with mefenamic acid, citalopram, trimipramine, and venlafaxine increased as the ingested dose increased. Conclusions. Antidepressants were frequently associated with seizures in overdose, but other pharmaceuticals, as mefenamic acid, were also associated with seizures in a considerable number of cases. Bupropion was the pharmaceutical with the highest seizure potential even if overdose with bupropion was uncommon in our sample. Adolescents might be more susceptible to seizures after mefenamic acid overdose than adults.“Part of this work is already published as a conference abstract for the XXXIV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 27–30 May 2014, Brussels, Belgium.” 8, Clin Toxicol 2014;52(4):298.

Phase reversal technique decreases cortical stimulation time during motor mapping

Neurophysiologic mapping of the primary motor cortex (PMC) is commonly used in supratentorial surgery. Electrical cortical stimulation is guided by anatomic landmarks towards the precentral gyrus, with recording of the triggered primary motor responses (TPMR) in the contralateral hemibody. Thus, factors such as distortion of the pericentral anatomy, small surgical fields, brain shifts and miscalibrated neuronavigational systems may lengthen the process and result in unnecessary stimulations, increasing the probability of triggering seizures. We hypothesized that central sulcus localization via the median somatosensory evoked potentials phase reversal technique (MSSEP PRT) accurately guides the surgeon, resulting in prompt identification of the PMC with minimal electrical stimulation. Multivariate Cox regression was used to study the impact of MSSEP PRT on time spent performing electrical cortical stimulation to TPMR. The analysis was adjusted for presence of increased cortical excitability, high motor thresholds, lesions close to PMC and fMRI data, in 100 consecutive standardized motor mapping procedures for brain tumor resection and epilepsy surgery. Phase reversal and change morphology of the recorded somatosensory evoked potentials quadrupled (hazard ratio [HR] 4.13, p<0.0001) and doubled (HR 2.14, p=0.02) the rate of obtaining TPMR, respectively. A 1mA increase in motor threshold decreased the rate by 9% (HR 0.91, p=0.0002). Afterdischarges triggered before TPMR and lesions in close proximity to PMC decreased the rate of TPMR by 76% (HR 0.23, p<0.0001) and 48% (HR 0.52, p=0.04), respectively. Informative PRT decreases stimulation time. Afterdischarges triggered before TPMR, high motor thresholds and lesions close to the PMC increase it.

Cognitive performance and convulsion risk after experimentally-induced febrile-seizures in rat

Many reports indicated that small percentage of children with febrile seizures develop epilepsy and cognitive disorders later in adulthood. In addition, the neuronal network of the hippocampus was reported to be deranged in adult animals after being exposed to hyperthermia-induced seizures in their neonatal life. The aims of this study were to investigate (1) latency and probability of seizures, (2) spatial learning and memory, in adult rats after neonatal hyperthermia-induced febrile seizures (FS). Prolonged FS were elicited in 10-day old, male Sprague Dawleys (n=11/group) by exposure to heated air (48–52°C) for 30min; control rats were exposed to 30°C air. After 1.5 months the animal's cognitive performance was assessed by 5 day trial in the Morris water maze. In another experiment the latency and probability of seizures were measured in response to pentylenetetrazole (PTZ) injections (increased doses ranged from 7 to 140mg/kg; i.p.). In water maze, both groups showed improvements in escape latency and distance swam to reach the platform; effects were significantly greater in control versus hyperthermia-treated animals on days 3 and 4. Latency and probability of PTZ-induced seizures were shorter and higher respectively, in hyperthermia-treated animals compared to controls. We concluded that FS in neonatal rats leads to enhanced susceptibility for seizures, as well as cognitive deficits in adults.

Levetiracetam versus (fos)phenytoin for seizure prophylaxis in pediatric patients with intracranial hemorrhage

Seizure prophylaxis is used in a variety of conditions, including supratentorial intracranial hemorrhage (ICH). In adults, studies have demonstrated phenytoin as the drug of choice for seizure prophylaxis; in children, levetiracetam is often provided due to its favorable side effect profile and pharmacokinetics. This study evaluated the difference in efficacy between these treatment options. This retrospective review included 126 patients between 1 month and 17 years of age with acute supratentorial ICH; all received seizure prophylaxis. Demographic data and outcome assessments were compared. Seizure prophylaxis was provided with (fos)phenytoin in 40 children, levetiracetam in 61 children, and both drugs in 25 patients. Baseline characteristics of the treatment groups were similar, except that more patients treated with (fos)phenytoin had seizures on presentation. Patients treated solely with (fos)phenytoin had a higher probability of early seizures (within 7 days of ICH) compared with those treated only with LVT, controlling for relevant variables including seizures on presentation (OR 24.6, p = 0.002). Patients treated with (fos)phenytoin were more likely to need additional antiepileptic drugs for seizure control (p = 0.005). There was no significant difference in the incidence of late seizures (> 7 days after ICH) (p = 0.265). Adverse events necessitating a change in therapy were uncommon. Levetiracetam is a reasonable alternative to (fos)phenytoin for prophylaxis of early posthemorrhagic seizures. Levetiracetam and (fos)phenytoin are well tolerated in children. Prospective studies are needed to determine superiority, optimal dosing, and impact on long-term outcomes.

Robust neonatal EEG seizure detection through adaptive background modeling.

Adaptive probabilistic modeling of the EEG background is proposed for seizure detection in neonates with hypoxic ischemic encephalopathy. The decision is made based on the temporal derivative of the seizure probability with respect to the adaptively modeled level of background activity. The robustness of the system to long duration "seizure-like" artifacts, in particular those due to respiration, is improved. The system was developed using statistical leave-one-patient-out performance assessment, on a large clinical dataset, comprising 38 patients of 1479 h total duration. The developed technique was then validated by a single test on a separate totally unseen randomized prospective dataset of 51 neonates totaling 2540 h of duration. By exploiting the proposed adaptation, the ROC area is increased from 93.4% to 96.1% (41% relative improvement). The number of false detections per hour is decreased from 0.42 to 0.24, while maintaining the correct detection of seizure burden at 70%. These results on the unseen data were predicted from the rigorous leave-one-patient-out validation and confirm the validity of our algorithm development process.

Early Surgical Therapy for Drug-Resistant Temporal Lobe Epilepsy

Despite reported success, surgery for pharmacoresistant seizures is often seen as a last resort. Patients are typically referred for surgery after 20 years of seizures, often too late to avoid significant disability and premature death. We sought to determine whether surgery soon after failure of 2 antiepileptic drug (AED) trials is superior to continued medical management in controlling seizures and improving quality of life (QOL). The Early Randomized Surgical Epilepsy Trial (ERSET) is a multicenter, controlled, parallel-group clinical trial performed at 16 US epilepsy surgery centers. The 38 participants (18 men and 20 women; aged ≥12 years) had mesial temporal lobe epilepsy (MTLE) and disabling seizues for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs. Eligibility for anteromesial temporal resection (AMTR) was based on a standardized presurgical evaluation protocol. Participants were randomized to continued AED treatment or AMTR 2003-2007, and observed for 2 years. Planned enrollment was 200, but the trial was halted prematurely due to slow accrual. Receipt of continued AED treatment (n = 23) or a standardized AMTR plus AED treatment (n = 15). In the medical group, 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery. The primary outcome variable was freedom from disabling seizures during year 2 of follow-up. Secondary outcome variables were health-related QOL (measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 [QOLIE-89] overall T-score), cognitive function, and social adaptation. Zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure free during year 2 of follow-up (odds ratio = ∞; 95% CI, 11.8 to ∞; P < .001). In an intention-to-treat analysis, the mean improvement in QOLIE-89 overall T-score was higher in the surgical group than in the medical group but this difference was not statistically significant (12.6 vs 4.0 points; treatment effect = 8.5; 95% CI, -1.0 to 18.1; P = .08). When data obtained after surgery from participants in the medical group were excluded, the effect of surgery on QOL was significant (12.8 vs 2.8 points; treatment effect = 9.9; 95% CI, 2.2 to 17.7; P = .01). Memory decline (assessed using the Rey Auditory Verbal Learning Test) occurred in 4 participants (36%) after surgery, consistent with rates seen in the literature; but the sample was too small to permit definitive conclusions about treatment group differences in cognitive outcomes. Adverse events included a transient neurologic deficit attributed to a magnetic resonance imaging-identified postoperative stroke in a participant who had surgery and 3 cases of status epilepticus in the medical group. Among patients with newly intractable disabling MTLE, resective surgery plus AED treatment resulted in a lower probability of seizures during year 2 of follow-up than continued AED treatment alone. Given the premature termination of the trial, the results should be interpreted with appropriate caution. clinicaltrials.gov Identifier: NCT00040326.

Seizure probability in animal models of acquired epilepsy: A perspective on the concept of the preictal state

The concept of a preictal state is based on the belief that it may be possible to predict seizures before they occur. The preictal state is viewed as a time period when a seizure is practically inevitable, or at least a period of greatly increased seizure probability. Changes in seizure frequency may provide insight into how seizure probability increases after brain injury. Here, time-dependent changes in the frequency of spontaneous recurrent seizures after brain injury are summarized from published, nearly continuous, electrographic (EEG) recordings of kainate-treated rats and neonatal rats subjected to hypoxia-ischemia. For these animal models, seizure frequency - and thus seizure probability - was a sigmoid function of time after the brain injury. This observation differs from the traditional view, where the development of epilepsy after brain injury is a step-function of time, and the latent period is the time between a brain injury and the first spontaneous seizure. Based on backward extrapolation of the plots of seizure frequency versus time, these data suggest that seizure probability increases continuously during the latent period. Also, spontaneous recurrent seizures frequently occurred in clusters, suggesting that the intra-cluster seizure intervals are periods of high seizure probability. Thus, seizure probability progressively increases as a function of time after an epileptogenic brain injury, and is particularly high between seizures within a cluster, as compared to the time between clusters. These data suggest that the detectors of the preictal state need to be accurate (and tested) over a very wide range of seizure probabilities, and that studies on the physiological events that occur during seizure clusters may provide insight on the properties of the preictal state.

Epilepsy after subarachnoid hemorrhage: the frequency of seizures after clip occlusion or coil embolization of a ruptured cerebral aneurysm

The aim of this study was to determine the probability of seizures after treatment of a ruptured cerebral aneurysm by clip occlusion and coil embolization, and to identify the risks and predictors of seizures over the short- and long-term follow-up period. The study population included 2143 patients with ruptured intracranial aneurysms who were enrolled in 43 centers and randomly assigned to clip application or coil placement. Those patients suffering a seizure were identified prospectively at various time points after randomization, as follows: before treatment; after treatment and before discharge; after discharge to 1 year; and annually thereafter. Two hundred thirty-five (10.9%) of the 2143 patients suffered a seizure after randomization; 89 (8.3%) of 1073 and 146 (13.6%) of 1070 in the endovascular and neurosurgical allocations, respectively (p = 0.014). In 19 patients the seizure was associated with a rehemorrhage. Of those patients who underwent coil placement alone, without additional procedures, 52 suffered a seizure, and in the group with clip occlusion alone, 91 patients suffered a seizure. The risk of a seizure after discharge in the endovascular group was 3.3% at 1 year and 6.4% at 5 years. In the neurosurgical group it was 5.2% at 1 year and 9.6% at 5 years. The risk of seizure was significantly greater in the neurosurgical group at both 2 years and at up to 14 years (p = 0.005 and p = 0.013, respectively). The significant predictors of increased risk were as follows: neurosurgical treatment allocation, hazard ratio (HR) 1.64 (95% CI 1.19-2.26); younger age, HR 1.54 (95% CI 1.14-2.13); Fisher grade > 1 on CT scans, HR 1.34 (95% CI 0.62-2.87); delayed ischemic neurological deficit due to vasospasm, HR 2.10 (95% CI 1.49-2.94); and thromboembolic complication, HR 5.08 (95% CI 3.00-8.61). A middle cerebral artery (MCA) aneurysm location was also a significant predictor of increased risk in both groups; the HR was 2.23 (95% CI 1.57-3.17), with the probability of seizure at 6.1% and 11.5% at 1 year in the endovascular and neurosurgery groups, respectively. The risk of seizures after coil embolization is significantly lower than that after clip occlusion. An MCA aneurysm location increased the risk of seizures in both groups.

The effect of decontamination procedures on the pharmacodynamics of venlafaxine in overdose.

To investigate the relationship between decontamination procedures and seizure events caused by venlafaxine overdose and to estimate the time at which 90% of patients would have had their first seizure in the presence and absence of decontamination. Data were collected from 319 patients who took an overdose of venlafaxine on 436 occasions. Seizures occurred on 24 of 436 occasions (5%). Patients received one of single dose activated charcoal (SDAC), whole bowel irrigation (WBI), a combination of either (SDAC/WBI) or no decontamination. Logistic regression and time to event analysis were used to investigate the influence of dose and decontamination on the probability of seizures and time to 90% (t(90) ) of seizure, respectively. A linear logistic regression model described the data. Simulation from the model showed that the probability of seizure was 0.05 (0.03-0.08), 0.19 (0.09-0.35) and 0.75 (0.30-0.96) at 1000, 5000 and 10 000 mg, respectively (median and 95% credible interval). At the mean dose of 2100 mg the odds ratios (OR) in the presence of SDAC, WBI and SDAC/WBI were 0.48 (0.25-0.89), 0.71 (0.35-1.22) and 0.25 (0.08-0.62), respectively. A modified Gompertz model described the time to seizure events. Simulations from the Gompertz model showed that the t(90) values for first seizure was 26 h and was not affected by dose or decontamination procedure. SDAC/WBI provided greater benefits than the sum of the independent effects of SDAC and WBI. Patients should be observed for at least 24 h for seizures based on the dose and risk of seizure occurring.

Limitations of Threshold-Based Brain Oxygen Monitoring for Seizure Detection

Brain tissue oxygen (PbtO(2)) monitors are utilized in a threshold-based fashion, triggering actions based on the presumption of tissue compromise when PbtO(2) is less than 20mmHg. Some early published practice guidelines suggest that seizure is a potential culprit when PbtO(2) crosses this threshold; evidence for this is not well defined. Data were collected manually as part of a prospective observational database. PbtO(2) monitors and continuous electroencephalogram (cEEG) were placed by clinical protocol in aneurysmal subarachnoid hemorrhage (aSAH) or traumatic brain injury (TBI) patients with a Glasgow Coma Scale (GCS)≤8. Eight patients with discrete seizures during an overlapping monitored period were identified. Probability of seizure when PbtO(2) value was <20mmHg (and the inverse) were calculated. There were 343 distinct seizure episodes and 1797 PbtO(2) measurements. 8.9% of seizures were followed by a PbtO(2) value below 20mmHg. Of all observed low PbtO(2) values, 3.8% were associated with seizure. Seizure length did not influence PbtO(2). Two patients with the highest number of seizures developed low PbtO(2) values post-seizure. Seizures were neither associated with a PbtO(2) value of <20mmHg nor associated with a drop in PbtO(2) value across a clinically significant threshold. However, we cannot rule out the existence of any relationship between PbtO(2) and seizure with this limited data set. Prospective research using electronically recorded data is required to more effectively examine the relationship between PbtO(2) and seizure.

Progressive NKCC1-Dependent Neuronal Chloride Accumulation during Neonatal Seizures

Seizures induce excitatory shifts in the reversal potential for GABA(A)-receptor-mediated responses, which may contribute to the intractability of electro-encephalographic seizures and preclude the efficacy of widely used GABAergic anticonvulsants such as phenobarbital. We now report that, in intact hippocampi prepared from neonatal rats and transgenic mice expressing Clomeleon, recurrent seizures progressively increase the intracellular chloride concentration ([Cl(-)](i)) assayed by Clomeleon imaging and invert the net effect of GABA(A) receptor activation from inhibition to excitation assayed by the frequency of action potentials and intracellular Ca(2+) transients. These changes correlate with increasing frequency of seizure-like events and reduction in phenobarbital efficacy. The Na(+)-K(+)-2Cl(-) (NKCC1) cotransporter blocker bumetanide inhibited seizure-induced neuronal Cl(-) accumulation and the consequent facilitation of recurrent seizures. Our results demonstrate a novel mechanism by which seizure activity leads to [Cl(-)](i) accumulation, thereby increasing the probability of subsequent seizures. This provides a potential mechanism for the early crescendo phase of neonatal seizures.

Increased coupling and altered glutamate transport currents in astrocytes following kainic-acid-induced status epilepticus

Profound astrogliosis coincident with neuronal cell loss is universally described in human and animal models of temporal lobe epilepsy (TLE). In the kainic acid-induced status epilepticus (SE) model of TLE, astrocytes in the hippocampus become reactive soon after SE and before the onset of spontaneous seizures. To determine if astrocytes in the hippocampus exhibit changes in function soon after SE, we recorded from SR101-labeled astrocytes using the whole-cell patch technique in hippocampal brain slices prepared from control and kainic-acid-treated rats. Glutamate transporter-dependent currents were found to have significantly faster decay time kinetics and in addition, dye coupling between astrocytes was substantially increased. Consistent with an increase in dye coupling in reactive astrocytes, immunoblot experiments demonstrated a significant increase in both glial fibrillary acidic protein (GFAP) and connexin 43, a major gap junction protein expressed by astrocytes. In contrast to what has been observed in resected tissue from patients with refractory epilepsy, changes in potassium currents were not observed shortly after KA-induced SE. While many changes in neuronal function have been identified during the initial period of low seizure probability in this model of TLE, the present study contributes to the growing body of literature suggesting a role for astrocytes in the process of epileptogenesis.

Subsequent Afebrile Seizure in Children Who Have a First Seizure With Fever After 6 Years of Age

The objective was to evaluate the risk and the risk factors associated with subsequent afebrile seizures in 31 children who experienced their first seizure with fever after 6 years of age. The children were classified into two groups. Group I comprised children with their first seizure with fever after 6 years of age (n = 15). Group II comprised children who had febrile seizures before 5 years of age and who had recurrent seizures with fever after 6 years of age (n = 16). Of these 31 children, 7 (22.5%) had subsequent afebrile seizure. The cumulative probability of subsequent afebrile seizure was 13.3% at 6 months and 36 months in group I; in group II, the cumulative probability was 12.5% at 6 months, 18.8% at 18 months, 25% at 24 months, and 31.3% at 36 months. There was no significant difference in the risk for subsequent afebrile seizures between the two groups. There were no risk factors associated with an increased risk of subsequent afebrile seizures. If the first seizure with fever occurred after 6 years of age, this was a significant risk for subsequent afebrile seizure; the risk of seizure recurrence in this group appears to be similar to children who have persistent febrile seizures after 6 years of age, but far below that of children with first epileptic seizure.

When is a postoperative seizure equivalent to “epilepsy recurrence” after epilepsy surgery?

Up to one-half of epilepsy surgery patients will have at least one seizure after surgery. We aim to characterize the prognosis following a first postoperative seizure, and provide criteria allowing early identification of recurrent refractory epilepsy. Analyzing 915 epilepsy surgery patients operated on between 1990 and 2007, we studied 276 who had >or=1 seizure beyond the immediate postoperative period. The probability of subsequent seizures was calculated using survival analysis. Patients were divided into seizure-free (no seizures for >or=1 year) and refractory (persistent seizures) and analyzed using multivariate regression analysis. After a first seizure, 50% had a recurrence within 1 month and 77% within a year before the risk slowed down to additional 2-3% increments every two subsequent years. After a second seizure, 50% had a recurrence within 2 weeks, 78% within 2 months, and 83% within 6 months. Having both the first and second seizures within six postoperative months [odds ratio (OR) 4.04; 95% confidence interval (CI) 2.05-8.40; p = 0.0001], an unprovoked initial recurrence (OR 3.92; 95% CI 2.13-7.30; p < 0.0001), and ipsilateral spikes on a 6-months postoperative electroencephalography (EEG) (OR 2.05; 95% CI 1.10-3.88; p = 0.025) predicted a poorer outcome, with 95% of patients who had all three risk factors becoming refractory. All patients with cryptogenic epilepsy and recurrent seizures developed refractoriness. Seizures will recur in most patients who present with their first postoperative event, with one-third eventually regaining seizure-freedom. Etiology and early and unprovoked postoperative seizures with epileptiform activity on EEG at six postoperative months may predict recurrent medical refractoriness.

The Minnesota Multiphasic Personality Inventory-2-Restructured Form in the epilepsy monitoring unit

The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a restructuring of the MMPI-2 that has improved the psychometric characteristics of the test. The primary aim of this study was to provide diagnostic utility data on the MMPI-2-RF in an epilepsy monitoring unit population ( N = 429). Mean comparisons revealed group differences on Validity Scales Fs and FBS-r; Restructured Clinical Scales RC1 and RC3; and Somatic Scales MLS, GIC, HPC, and NUC. Diagnostic utility data are provided for those scales with the largest effect sizes: RC1, FBS-r, and NUC. On RC1, sensitivity was 76% and specificity was 60%, similar to values found when applying published decision rules to the MMPI-2. RC1 explains unique variance in diagnosis beyond that explained by demographic or medical history risk factors. We provide likelihood ratios for scores on RC1, FBS-r, and NUC that can be used by the clinician to calculate posttest odds and probability of nonepileptic seizures using the base rate of nonepileptic seizures in his/her population.