Refractory Epilepsy Patients Research Articles

Lateralizing value of unilateral relative ictal immobility in patients with refractory focal seizures – Looking beyond unilateral automatisms

PurposeIctal motor phenomena play a crucial role in the localization of seizure focus in the management of refractory focal epilepsy. While the importance of unilateral automatisms is well established, little attention is paid to the contralateral relatively immobile limb. In cases where automatisms mimic clonic or dystonic movements and in the absence of previously well-established signs, unilateral relative ictal immobility (RII) is potentially useful as a lateralizing sign. This study was carried out to examine the lateralizing value of this sign and to define its characteristics among patients of refractory focal epilepsy. MethodsVEEGs of 69 consecutive patients of refractory focal epilepsy who had undergone epilepsy surgery at our center over last four years were reviewed and analyzed for the presence of RII. Unilateral RII was defined as a paucity of movement in one limb lasting for at least 10s while the contralateral limb showed purposive or semi-purposive movements (in the absence of tonic or dystonic posturing or clonic movements in the involved limb). The findings were seen in the light of VEEG, radiological and nuclear imaging data, and with post-surgical outcome. ResultsUnilateral RII as a lateralizing sign was found in 24 of 69 patients (34.78%), consisting of both temporal and extra temporal epilepsy, with 100% concordance with VEEG and MRI data. All patients demonstrating this sign had a good post-surgical outcome. ConclusionRII, when well characterized is a frequent and reliable lateralizing sign in patients of refractory focal epilepsy.

Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses

ObjectiveSingle Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100ms) that map cortical connectivity. We analyzed properties of ERs, including frequencies >80Hz, in the SOZ and seizure propagation areas. MethodsWe used data from 12 refractory epilepsy patients. SPES consisted of 10 pulses of 1ms, 4–8mA and 5s interval on adjacent electrodes pairs. Data were available at 2048samples/s for six and 512samples/s (22 bits) for eight patients and analyzed in the time–frequency (TF) and time-domain (TD). ResultsElectrodes with ERs were stronger associated with SOZ than non-SOZ electrodes. ERs with frequency content >80Hz exist and are specific for SOZ channels. ERs evoked by stimulation of seizure onset electrodes were associated with electrodes involved in seizure propagation. ConclusionAnalysis of ERs can reveal aspects of pathology, manifested by association with seizure propagation and areas with high ER numbers that coincide with the SOZ. SignificanceNot only DRs, but also ERs could have clinical value for mapping epileptogenic cortex and help to unravel aspects of the epileptic network.

Online detection of tonic-clonic seizures in pediatric patients using ECG and low-complexity incremental novelty detection.

Home monitoring of refractory epilepsy patients has become of more interest the last couple of decades. A biomedical signal that can be used for online seizure detection at home is the electrocardiogram. Previous studies have shown that tonic-clonic seizures are most often accompanied with a strong heart rate increase. The main issue however is the strong patient-specific behavior of the ictal heart rate features, which makes it hard to make a patient-independent seizure detection algorithm. A patient-specific algorithm might be a solution, but existing methods require the availability of data of several seizures, which would make them inefficient in case the first seizure only occurs after a couple of days. Therefore an online method is described here that automatically converts from a patient-independent towards a patient-specific algorithm as more patient-specific data become available. This is done by using online feedback from the users to previously given alarms. By using a simplified one-class classifier, no seizure training data needs to be available for a good performance. The method is already able to adapt to the patient-specific characteristics after a couple of hours, and is able to detect 23 of 24 seizures longer than 10s, with an average of 0.38 false alarms per hour. Due to its low-complexity, it can be easily used for wearable seizure detection at home.

Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy.

Under an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children. Of the 25 subjects in the trial, 13 were being treated with clobazam (CLB). Because CLB and CBD are both metabolized in the cytochrome P450 (CYP) pathway, we predicted a drug-drug interaction, which we evaluate in this article. Thirteen subjects with refractory epilepsy concomitantly taking CLB and CBD under IND 119876 were included in this study. Demographic information was collected for each subject including age, sex, and etiology of seizures, as well as concomitant antiepileptic drugs (AEDs). CLB, N-desmethylclobazam (norclobazam; nCLB), and CBD levels were measured over the course of CBD treatment. CLB doses were recorded at baseline and at weeks 4 and 8 of CBD treatment. Side effects were monitored. We report elevated CLB and nCLB levels in these subjects. The mean (±standard deviation [SD]) increase in CLB levels was 60±80% (95% confidence interval (CI) [-2-91%] at 4weeks); the mean increase in nCLB levels was 500±300% (95% CI [+90-610%] at 4weeks). Nine of 13 subjects had a >50% decrease in seizures, corresponding to a responder rate of 70%. The increased CLB and nCLB levels and decreases in seizure frequency occurred even though, over the course of CBD treatment, CLB doses were reduced for 10 (77%) of the 13 subjects. Side effects were reported in 10 (77%) of the 13 subjects, but were alleviated with CLB dose reduction. Monitoring of CLB and nCLB levels is necessary for clinical care of patients concomitantly on CLB and CBD. Nonetheless, CBD is a safe and effective treatment of refractory epilepsy in patients receiving CLB treatment.

Anterior temporal lobectomy compared with laser thermal hippocampectomy for mesial temporal epilepsy: A threshold analysis study

PurposeAnterior Temporal Lobectomy (ATL) is the gold standard surgical treatment for refractory temporal lobe epilepsy (TLE), but it carries the risks associated with invasiveness, including cognitive and visual deficits and potential damage to eloquent structures. Laser thermal hippocampectomy (LTH) is a new procedure that offers a less invasive alternative to the standard open approach. In this decision analysis, we determine the seizure freedom rate at which LTH would be equivalent to ATL. MethodsMEDLINE searches were performed for studies of ATL from 1995 to 2014. Using complication and success rates from the literature, we constructed a decision analysis model for treatment with ATL and LTH. Quality-adjusted life years (QALYs) were derived from examining patient preferences in similar clinical conditions. LTH data were obtained from a preliminary multicenter study report following patients for 6–12 months. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used. Results350 studies involving 25,144 cases of ATL were included. Outcomes of LTH were taken from a recently presented multicenter series of 68 cases. Over a 10-year postoperative modeling period, LTH value was 5.9668 QALYs and ATL value was 5.8854. Sensitivity analysis revealed that probabilities of seizure control and late morbidity of LTH are most likely to affect outcomes compared to ATL. We calculated that LTH would need to stop disabling seizures (Engel class I) in at least 43% of cases and have fewer than 40% late mortality/morbidity to result in quality of life at least as good as that after ATL. ConclusionsThis decision analysis based on early follow-up data suggests LTH has similar utility to ATL. These early data support LTH as a potentially comparable less invasive alternative to ATL in refractory TLE. LTH utility may remain comparable to ATL even if long-term seizure control is less than that of ATL. Larger prospective studies with long-term follow up will be needed to validate the true role of LTH in the refractory epilepsy patient population.

Effect of an Antiepileptic drug(AED) holiday in the Epilepsy monitoring unit (EMU) on subsequent seizure frequency after reinstituting in medically refractory epilepsy patients- a Prospective Observational Controlled Study (P4.272)

Effect of an Antiepileptic drug(AED) holiday in the Epilepsy monitoring unit (EMU) on subsequent seizure frequency after reinstituting in medically refractory epilepsy patients- a Prospective Observational Controlled Study (P4.272)

Functional connectivity of amygdala in refractory epilepsy:a resting-state functional study of magnetic resonance imaging

To explore the functions of amygdala functional connectivity in the pathogenesis of refractory epilepsy with resting-state functional magnetic resonance imaging (RS-fMRI). A total of 19 patients with refractory epilepsy were recruited from August 2013 to June 2014. And 19 healthy persons were selected as the controls.No obvious epileptogenic lesions of intracranial structures were found on multi-modal neuroimaging.Ictal and interictal epileptic activities on long-term video electroencephalogram (EEG) showed spine spread spike and wave in bilateral cerebral hemispheres. All fMRI data were preprocessed after RS-fMRI scanning. Then left and right amygdalas were selected as regions of interest (ROIs) for calculating the linear correlation between amygdala and whole brain. As relative to the control group, the changes of brain areas in functional connectivity were examined for the intractable epilepsy group. Compared with the controls, left amygdala in refractory epilepsy group showed increased functional connectivity with bilateral fusiform gyrus, bilateral calcarine gyrus and right lingual, on the contrary decreased functional connectivity with bilateral cuneus, bilateral precuneus, bilateral caudatas and left thalamus.However, right amygdala demonstrated increased functional connectivity with bilateral calcarine gyrus and bilateral linguals, but decreased functional connectivity with bilateral caudatas and left putamen (P < 0.05). Altered functional connectivity of amygdala reflects its dysfunction in refractory epilepsy patients. It suggested that amygdala is an important component of "epileptic network" participating in the occurrence and development of refractory epilepsy.

Lacosamide use in the treatment of refractory epilepsy in tuberous sclerosis complex

Lacosamide (LCS) was approved by the United States Food and Drug Administration (FDA) in 2008 as adjunctive therapy to other anti-epileptic drugs (AEDs) to treat focal-onset seizures, with or without secondary generalization. Its role in the treatment of epilepsy in individuals with tuberous sclerosis complex (TSC) has yet to be determined. This study evaluates LCS treatment of focal-onset refractory epilepsy in patients with TSC. From November 2009 to June 2014, 46 TSC patients followed by a single neurologist were treated with LCS. Forty-eight percent were responders (seizure reduction ≥50%). No significant differences between responders and non-responders in demographic characteristics were found. LCS appears to be an effective and safe treatment of refractory focal onset seizures in TSC. Determining the long-term tolerability and efficacy of LCS in TSC patients requires additional clinical experience.

Long-term effective rate, retention rate and tolerability of the ketogenic diet in paediatrics drug-resistant epilepsies

Objective To evaluate the long-term effective rate, retention rate and tolerability of the ketogenic diet (KD) in pediatric drug-resistant epilepsies. Methods Data of 36 children who were treated in Department of Pediatrics, the Second Affiliated Hospital of Xi'an Jiaotong University from Nov.2011 to Dec.2013 and had continuous follow-up of at least 12 months after initiation of the KD were analyzed prospectively.Response was defined as 50% seizure reduction.The effective rate, retention rate, outcome-predictive value of various clinical factors were also assessed.The causes of the patients withdrew from KD and side effects were recorded and analyzed. Results Thirty-six children(29 boys, 7 girls; mean age of 2.84 years)were included.The effective rate was 50.0%, 52.8%, 47.2% and 41.7% at the 1, 3, 6, 12 months; the retention rate respectively was 94.4%, 91.2%, 69.4% and 52.8%.Seventeen cases withdrew from KD.Seven cases (41.2%)ceased KD because of a lack of compliance, 5 patients because of poor outcome, and 2 cases because of repeated infection.None of the age, disease duration, etiology and seizure type could be used as the predictor for the favourable treatment for outcome.The antiepileptic drugs before KD might be predicted the efficacy of the KD.The less amount of the antiepileptic drugs, the more opportunity of the KD might have to succeed.The side effects on the start-up period were drowsiness, week and digestive discomfort, hyperlipoidemia, hypoglycemia and hepatic dysfunction.The side effects on the maintenance period were digestive discomfort, susceptibility to infection, hyperlipoidemia, the deficiency of trace elements. Conclusions The KD is a safe and potentially effective method in treatment of refractory epilepsy patients who do not respond to customary medication therapies. Key words: Ketogenic diet; Refractory epilepsy; Effective rate; Retention rate; Side effect

Effectiveness of levetiracetam use following resective surgery in patients with refractory epilepsy: A prospective observational study

This study aimed to evaluate the effectiveness of levetiracetam (LEV) use for seizure control in patients who had undergone resective surgery for intractable epilepsy in routine clinical practice. This was a prospective, observational study. Refractory epilepsy patients who underwent epilepsy surgery from January 2008 to December 2011 in the Department of Neurosurgery, West China Hospital were prospectively analyzed. Patients were divided into two groups according to antiepileptic drug (AED) treatment used immediately after epilepsy surgery (group A: therapy with LEV; group B: therapy without LEV). AED regimens were compared with regard to seizure-outcome for a period of more than 2 years. The International League Against Epilepsy (ILAE) classification was used to categorize seizure outcome. A total of 319 patients (184 male and 135 female patients; mean age 28.2±13.4 years) were studied. The mean postoperative follow-up period was 3.9±1.2 years. The two groups showed was no significant difference in preoperative baseline data. At the 6-month follow-up, the proportion of patients with seizure freedom was significantly higher in group A than in group B (78.8% vs. 67.5%, p=0.03). Seizure outcomes after 2 years were assessed using the ILAE classification. The proportion of patients under ILAE seizure-outcome classification I (seizure freedom) was significantly higher in group A than in group B (74.3% vs. 60.7%, p=0.01). Seizure recurrence rates at the final assessment, after planned reduction or withdrawal, were 26.3% for group A and 40.6% for group B (p=0.04). AED strategy after resective surgery may be a potentially modifiable prognostic indicator influencing seizure outcome in patients with intractable epilepsy. Compared to other AEDs, LEV appears to be more effective in controlling postoperative seizures in our long-term follow-up, and the advantage can be seen in early stage after surgery.

Early prediction of medication refractoriness in children with idiopathic epilepsy based on scalp EEG analysis.

Refractory epilepsy often has deleterious effects on an individual's health and quality of life. Early identification of patients whose seizures are refractory to antiepileptic drugs is important in considering the use of alternative treatments. Although idiopathic epilepsy is regarded as having a significantly lower risk factor of developing refractory epilepsy, still a subset of patients with idiopathic epilepsy might be refractory to medical treatment. In this study, we developed an effective method to predict the refractoriness of idiopathic epilepsy. Sixteen EEG segments from 12 well-controlled patients and 14 EEG segments from 11 refractory patients were analyzed at the time of first EEG recordings before antiepileptic drug treatment. Ten crucial EEG feature descriptors were selected for classification. Three of 10 were related to decorrelation time, and four of 10 were related to relative power of delta/gamma. There were significantly higher values in these seven feature descriptors in the well-controlled group as compared to the refractory group. On the contrary, the remaining three feature descriptors related to spectral edge frequency, kurtosis, and energy of wavelet coefficients demonstrated significantly lower values in the well-controlled group as compared to the refractory group. The analyses yielded a weighted precision rate of 94.2%, and a 93.3% recall rate. Therefore, the developed method is a useful tool in identifying the possibility of developing refractory epilepsy in patients with idiopathic epilepsy.

The prognosis of refractory epilepsy patients rejected from epilepsy surgery.

Up to one-third of individuals diagnosed as having epilepsy continue to have seizures despite appropriate anti-epileptic drug treatment. These patients are often referred for presurgical evaluation, and many are rejected from focal resective surgery due to medical reasons or, alternatively, they choose not to undergo it. We compared the outcomes and characteristics of the non-operated patients who continued on medical therapy alone with those who underwent vagus nerve stimulator (VNS) implantation in addition to medical therapy. The medical records of consecutive adult patients referred for presurgical evaluation for suitability for epilepsy surgery in the Tel-Aviv Sourasky Medical Center between 2007 and 2011 and were rejected from or decided against surgery were reviewed. Updated information on seizure frequency was supplemented by telephone interviews between April and July, 2013. Fifty-two patients who continued solely on medical therapy and 35 patients who additionally underwent VNS implantation were included in the study. Forty-seven of the former and 33 of the latter agreed to be interviewed. There was a significant improvement in the seizure frequency between the time of the presurgical evaluation and the time of the interview in both groups. Eight medically treated patients (17%) and 2 patients who also underwent VNS implantation (6%) reported being seizure-free during the preceding 3 months. A considerable minority of patients with refractory epilepsy who were rejected or chose not to undergo epilepsy surgery may improve over time and even become seizure-free following adjustment of anti-epileptic drugs with or without concomitant VNS.

Sensitivity and Specificity of Interictal EEG-fMRI for Detecting the Ictal Onset Zone at Different Statistical Thresholds.

There is currently a lack of knowledge about electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) specificity. Our aim was to define sensitivity and specificity of blood oxygen level dependent (BOLD) responses to interictal epileptic spikes during EEG-fMRI for detecting the ictal onset zone (IOZ). We studied 21 refractory focal epilepsy patients who had a well-defined IOZ after a full presurgical evaluation and interictal spikes during EEG-fMRI. Areas of spike-related BOLD changes overlapping the IOZ in patients were considered as true positives; if no overlap was found, they were treated as false-negatives. Matched healthy case-controls had undergone similar EEG-fMRI in order to determine true-negative and false-positive fractions. The spike-related regressor of the patient was used in the design matrix of the healthy case-control. Suprathreshold BOLD changes in the brain of controls were considered as false positives, absence of these changes as true negatives. Sensitivity and specificity were calculated for different statistical thresholds at the voxel level combined with different cluster size thresholds and represented in receiver operating characteristic (ROC)-curves. Additionally, we calculated the ROC-curves based on the cluster containing the maximal significant activation. We achieved a combination of 100% specificity and 62% sensitivity, using a Z-threshold in the interval 3.4–3.5 and cluster size threshold of 350 voxels. We could obtain higher sensitivity at the expense of specificity. Similar performance was found when using the cluster containing the maximal significant activation. Our data provide a guideline for different EEG-fMRI settings with their respective sensitivity and specificity for detecting the IOZ. The unique cluster containing the maximal significant BOLD activation was a sensitive and specific marker of the IOZ.

Deep brain and cortical stimulation for epilepsy.

Despite optimal medical treatment, including epilepsy surgery, many epilepsy patients have uncontrolled seizures. In the last decades, interest has grown in invasive intracranial neurostimulation as a treatment for these patients. Intracranial stimulation includes both deep brain stimulation (DBS) (stimulation through depth electrodes) and cortical stimulation (subdural electrodes). To assess the efficacy, safety and tolerability of deep brain and cortical stimulation for refractory epilepsy based on randomized controlled trials. We searched PubMed (6 August 2013), the Cochrane Epilepsy Group Specialized Register (31 August 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7 of 12) and reference lists of retrieved articles. We also contacted device manufacturers and other researchers in the field. No language restrictions were imposed. Randomized controlled trials (RCTs) comparing deep brain or cortical stimulation to sham stimulation, resective surgery or further treatment with antiepileptic drugs. Four review authors independently selected trials for inclusion. Two review authors independently extracted the relevant data and assessed trial quality and overall quality of evidence. The outcomes investigated were seizure freedom, responder rate, percentage seizure frequency reduction, adverse events, neuropsychological outcome and quality of life. If additional data were needed, the study investigators were contacted. Results were analysed and reported separately for different intracranial targets for reasons of clinical heterogeneity. Ten RCTs comparing one to three months of intracranial neurostimulation to sham stimulation were identified. One trial was on anterior thalamic DBS (n = 109; 109 treatment periods); two trials on centromedian thalamic DBS (n = 20; 40 treatment periods), but only one of the trials (n = 7; 14 treatment periods) reported sufficient information for inclusion in the quantitative meta-analysis; three trials on cerebellar stimulation (n = 22; 39 treatment periods); three trials on hippocampal DBS (n = 15; 21 treatment periods); and one trial on responsive ictal onset zone stimulation (n = 191; 191 treatment periods). Evidence of selective reporting was present in four trials and the possibility of a carryover effect complicating interpretation of the results could not be excluded in 4 cross-over trials without any washout period. Moderate-quality evidence could not demonstrate statistically or clinically significant changes in the proportion of patients who were seizure-free or experienced a 50% or greater reduction in seizure frequency (primary outcome measures) after 1 to 3 months of anterior thalamic DBS in (multi)focal epilepsy, responsive ictal onset zone stimulation in (multi)focal epilepsy patients and hippocampal DBS in (medial) temporal lobe epilepsy. However, a statistically significant reduction in seizure frequency was found for anterior thalamic DBS (-17.4% compared to sham stimulation; 95% confidence interval (CI) -32.1 to -1.0; high-quality evidence), responsive ictal onset zone stimulation (-24.9%; 95% CI -40.1 to 6.0; high-quality evidence) ) and hippocampal DBS (-28.1%; 95% CI -34.1 to -22.2; moderate-quality evidence). Both anterior thalamic DBS and responsive ictal onset zone stimulation do not have a clinically meaningful impact on quality life after three months of stimulation (high-quality evidence). Electrode implantation resulted in asymptomatic intracranial haemorrhage in 3% to 4% of the patients included in the two largest trials and 5% to 13% had soft tissue infections; no patient reported permanent symptomatic sequelae. Anterior thalamic DBS was associated with fewer epilepsy-associated injuries (7.4 versus 25.5%; P = 0.01) but higher rates of self-reported depression (14.8 versus 1.8%; P = 0.02) and subjective memory impairment (13.8 versus 1.8%; P = 0.03); there were no significant differences in formal neuropsychological testing results between the groups. Responsive ictal-onset zone stimulation was well tolerated with few side effects but SUDEP rate should be closely monitored in the future (4 per 340 [= 11.8 per 1000] patient-years; literature: 2.2-10 per 1000 patient-years). The limited number of patients preclude firm statements on safety and tolerability of hippocampal DBS. With regards to centromedian thalamic DBS and cerebellar stimulation, no statistically significant effects could be demonstrated but evidence is of only low to very low quality. Only short term RCTs on intracranial neurostimulation for epilepsy are available. Compared to sham stimulation, one to three months of anterior thalamic DBS ((multi)focal epilepsy), responsive ictal onset zone stimulation ((multi)focal epilepsy) and hippocampal DBS (temporal lobe epilepsy) moderately reduce seizure frequency in refractory epilepsy patients. Anterior thalamic DBS is associated with higher rates of self-reported depression and subjective memory impairment. SUDEP rates require careful monitoring in patients undergoing responsive ictal onset zone stimulation. There is insufficient evidence to make firm conclusive statements on the efficacy and safety of hippocampal DBS, centromedian thalamic DBS and cerebellar stimulation. There is a need for more, large and well-designed RCTs to validate and optimize the efficacy and safety of invasive intracranial neurostimulation treatments.

Epileptic seizure prediction using relative spectral power features

ObjectivePrediction of epileptic seizures can improve the living conditions for refractory epilepsy patients. We aimed to improve sensitivity and specificity of prediction methods, and to reduce the number of false alarms. MethodsRelative combinations of sub-band spectral powers of electroencephalogram (EEG) recordings across all possible channel pairs were utilized for tracking gradual changes preceding seizures. By using a specifically developed feature selection method, a set of best candidate features were fed to support vector machines in order to discriminate cerebral state as preictal or non-preictal. ResultsProposed algorithm was evaluated on continuous long-term multichannel scalp and invasive recordings (183 seizures, 3565h). The best results demonstrated a sensitivity of 75.8% (66 out of 87 seizures) and a false prediction rate of 0.1h−1. Performance was validated statistically, and was superior to that of analytical random predictor. ConclusionApplying machine learning methods on a reduced subset of proposed features could predict seizure onsets with high performance. SignificanceOur method was evaluated on long-term continuous recordings of overall about 5months, contrary to majority of previous studies using short-term fragmented data. It is of very low computational cost, while providing acceptable levels of alarm sensitivity and specificity.

Hippocampal slow EEG frequencies during NREM sleep are involved in spatial memory consolidation in humans.

The hypothesis that sleep is instrumental in the process of memory consolidation is currently largely accepted. Hippocampal formation is involved in the acquisition of declarative memories and particularly of spatial memories. Nevertheless, although largely investigated in rodents, the relations between spatial memory and hippocampal EEG activity have been scarcely studied in humans. Aimed to evaluate the effects of spatial learning on human hippocampal sleep EEG activity, we recorded hippocampal Stereo-EEG (SEEG) in a group of refractory epilepsy patients undergoing presurgical clinical evaluation, after a training on a spatial navigation task. We observed that hippocampal high-delta (2-4 Hz range) activity increases during the first NREM episode after learning compared to the baseline night. Moreover, the amount of hippocampal NREM high-delta power was correlated with task performance at retest. The effect involved only the hippocampal EEG frequencies inasmuch no differences were observed at the neocortical electrodes and in the traditional polysomnographic measures. The present findings support the crucial role of hippocampal slow EEG frequencies during sleep in the memory consolidation processes. More generally, together with previous results, they suggest that slow frequency rhythms are a fundamental characteristic of human hippocampal EEG during both sleep and wakefulness, and are related to the consolidation of different types of memories.

Expression of HIF-1α and MDR1/P-glycoprotein in refractory mesial temporal lobe epilepsy patients and pharmacoresistant temporal lobe epilepsy rat model kindled by coriaria lactone

Hypoxia-inducible factor-1α (HIF-1α) is thought to mediate pharmacoresistance in tumor by inducing Pgp overexpression. We aimed to investigate the expression of HIF-1α and MDR1/P-glycoprotein in refractory epilepsy, to explore the correlation of HIF-1α with epilepsy multidrug resistance. We collected hippocampus and mesial temporal lobe (MTL) cortex of refractory mesial temporal lobe epilepsy (mTLE) patients that underwent surgery, and established a pharmacoresistant TLE rat model kindled by coriaria lactone. We used real-time quantitative PCR (RQ-PCR) and western blot to investigate expression of HIF-1α and MDR1 in hippocampus and MTL/entorhinal cortex. We found that the expression of HIF-1α and MDR1, at both mRNA and protein levels, were up-regulated in hippocampus and MTL cortex of mTLE patients compared with the control cortex (all P < 0.05), and increased in hippocampus and entorhinal cortex of kindled rat model versus the control group (all P < 0.05). These results demonstrated the overexpression of HIF-1α and MDR1/Pgp in hippocampus and MTL/entorhinal cortex of mTLE patients and the pharmacoresistant TLE rat model. HIF-1α may have a regulatory effect on MDR1 expression in refractory epilepsy, which is probably consistent with MDR mechanism in tumor.

The association between periodontal disease and seizure severity in refractory epilepsy patients

PurposePeriodontal diseases are common in most populations and affect people at all socioeconomic levels. Evidence suggests that patients with epilepsy actually have higher risks of dental disease and increased oral health needs, but the frequency and consequences of poor controlled seizures on dental and periodontal health have not been reported before. We aimed to assess the impact of seizure frequency on periodontal status and oral hygiene in a sample of epilepsy patients. MethodsOne hundred and nine consecutive patients treated for epilepsy at the outpatient clinic of our University Hospital were invited to take part in an oral examination to determine their periodontal disease status, together with a control group. In addition, seizure frequency and use of medication were documented. ResultsIn logistic regression model, patients were significantly more susceptible to bad oral hygiene, gingivitis and periodontitis that controls (p<0.001); seizure frequency was significantly related to bad oral hygiene (p=0.010), gingivitis (p<0.001) and periodontitis (p<0.001). Tooth brushing habits and presence of caries were associated with oral health in patients group. ConclusionOur study found a significant positive correlation between periodontal disease and seizure severity. Epilepsy patients need to focus more on their oral health and quality of oral hygiene.

Comparison between Different ESI Methods on Refractory Epilepsy Patients Shows a High Sensitivity for Bayesian Model Averaging

Electrical Source Imaging (ESI) is a non-invasive technique of reconstructing brain activities using EEG data. This technique has been applied to evaluate epilepsy patients being evaluated for epilepsy surgery, showing encouraging results for mapping interictal epileptiform discharges (IED). However, ESI is underused in planning epilepsy surgery. This is basically due to the wide availability of methods for solving the electromagnetism inverse problem (e-IP) associated to few studies using EEG setups similar to those most commonly used in clinical setting. In this study, we applied six different methods of solving the e-IP based on IEDs of 20 focal epilepsy patients that presented abnormalities in their MRI. We compared the ESI maps obtained by each method with the location of the abnormality, calculating the Euclidian distances from the center of the lesion to the closest border of the method solution (CL-BM) and also to the solution’s maxima (CL-MM). We also applied a score system in order to allow us to evaluate the sensitivity of each method for temporal and extra temporal patients. In our patients, the Bayesian Model Averaging method had a sensitivity of 86% and the shortest CL-MM. This method also had more restricted solutions that were more representative of epileptogenic activities than those obtained by the other methods.

Chapter Ten - Modern Techniques of Epileptic Focus Localization

A clear concept of epileptic zones remains of high clinical relevance in presurgical evaluation of refractory epilepsy patients and in resection planning. Recent advances in understanding how each of the epileptic zones is functionally organized strengthened the importance of the network concept. It has been shown that neuronal networks underlying the individual epileptic zone may involve multiple brain structures with complex interactions between them. The network concept has impact not only for better understanding of pathophysiology of partial epilepsy but also for clinical practice, particularly for epilepsy surgery. This review examines recent reports on the use of advanced imaging techniques which enable to map the epileptic zones and their structural and functional organization. Magnetic resonance postprocessing substantially improved the accuracy in detection of the epileptogenic lesions. The seizure-onset zone is primarily determined by electrophysiology but can also be localized using single photon emission computed tomography. The functional deficit zone is commonly assessed by a number of tests including methods of functional neuroimaging (positron emission tomography) which can delineate hypometabolic cortical areas and subcortical structures. Hemodynamic fluctuations associated with interictal epileptiform discharges can be detected by novel functional magnetic resonance technique which is nowadays widely used for the irritative zone localization. These techniques open new prospect for epilepsy surgery in patients who were previously considered as not suitable candidates of surgical treatment.