Refractory Epilepsy Patients Research Articles

Anterior thalamic stimulation for intractable epilepsy

As per W.H.O. 50 million patients are suffering from epilepsy and out of them 80% are in developing countries. In India 1% of population suffer from epilepsy. 30% of these patients become refractory to medication and would require either surgery or deep brain stimulation. Deep brain stimulation is an established therapy for Parkinson disease, essential tremor and certain form of Dystonia. Recently it has been used in intractable epilepsy with good outcome in a SANTE clinical trial. The electrical stimulation of anterior thalamus can significantly reduce the number of seizures and can improve the quality of life. Based on both animal studies and clinical trials, we subjected six patients to anterior thalamic stimulation for medically refractory epilepsy. All six selected patients were not suitable for epilepsy surgery. The age ranged from 20 years to 53 years. Bilateral anterior thalamic stimulation was done in all cases using ZD stereotactic frame under general anaesthesia. The target was calculated using fused images of CT Scan and MRI. The placement of electrodes was confirmed by microelectrode recording (thalamic burst) and intra-operative driving response obtained by scalp EEG. The post-operative CT scan was done to confirm the position of electrodes.In three patients Medtronic DBS system (Activa PC) was used while other three patients have St Jute device (Libra) device. Anticonvulsant medications were kept unchanged. The programming was started after one week using electro encephalography. The reduction or abolition of inter-ectal discharges and eeg desynchronization was kept as goal of programming. All the patients were follow-up 6 months to 4 years. Significant seizure reduction observed immediately after programming. Two patients became seizure free. Three patients have 60–80% seizure control. One patient did not get significant benefit. In three patients (good respondent) after a period of two years seizure frequency increased following battery depletion that required replacement using respectable rechargeable DBS system. Above study shows effectiveness of anterior thalamic stimulation for intractable epilepsy. Better result can only be achieved by effective eeg guided programming. Prolonged follow-up with more number of cases is required to establish deep brain stimulation of anterior thalamic nuclei as safe and effective therapy for refractory epilepsy patients who are otherwise not suitable candidate for conventional epilepsy surgery.

373 Is Stereotacticelectroencephalography Safe? A Systematic Review and Meta-Analysis of Stereo-electroencephalography-Related Complications

INTRODUCTION:Stereotacticelectroencephalography (SEEG) is a procedure performed to define the epileptogenic zone in medically refractory epilepsy patients. Despite not requiring a craniotomy, intracerebral electrodes have gained a reputation of a “relatively high morbidity” associated with their pla

Elevated basal glutamate and unchanged glutamine and GABA in refractory epilepsy: Microdialysis study of 79 patients at the yale epilepsy surgery program.

Aberrant glutamate and γ-aminobutyric acid (GABA) neurotransmission contribute to seizure generation and the epileptic state. However, whether levels of these neurochemicals are abnormal in epileptic patients is unknown. Here, we report on interictal levels of glutamate, glutamine, and GABA in epilepsy patients at seizure onset and nonepileptic sites, cortical lesions, and from patients with poorly localized neocortical epilepsies. Subjects (n = 79) were medically refractory epilepsy patients undergoing intracranial electroencephalogram evaluation. Microdialysis probes (n = 125) coupled to depth electrodes were implanted within suspected seizure onset sites and microdialysis samples were obtained during interictal periods. Glutamate, glutamine, and GABA were measured using high-performance liquid chromatography. Probe locations were subsequently classified by consensus of expert epileptologists. Glutamate levels were elevated in epileptogenic (p = 0.03; n = 7), nonlocalized (p < 0.001), and lesional cortical sites (p < 0.001) when compared to nonepileptogenic cortex. Glutamate was also elevated in epileptogenic (p < 0.001) compared to nonepileptogenic hippocampus. There were no statistical differences in GABA or glutamine, although GABA levels showed high variability across patients and groups. Our findings indicate that chronically elevated extracellular glutamate is a common pathological feature among epilepsies with different etiology. Contrary to our predictions, GABA and glutamine levels were not decreased in any of the measured areas. Whereas variability in GABA levels may in part be attributed to the use of GABAergic antiepileptic drugs, the stability in glutamine across patient groups indicate that extracellular glutamine levels are under tighter metabolic regulation than previously thought. Ann Neurol 2016;80:35-45.

Effect factors for language and memory dominance evaluation in patients with refractory epilepsy

Objective To investigate the effect factors for language and memory dominance testing in propofol Wada test in refractory epilepsy patients. Methods From January 2010 to August 2013, total of 23 patients underwent propofol Wada tests for language and memory dominance evaluation.According the performance in language test and memory test, the patients were divided into two groups, respectively: succeed with test or failed in test.The relevant factors including age, duration of epilepsy, handedness, FIQ ( full scale of intelligence quotient ), lateralization of lesions, language dominance, dose of propofol and the adverse effects of propofol were recorded as independent variables.Logistic regression was adopted to screen the effect factors for memory dominance evaluation.All statistical analyses were processed with SPSS software. Results All 23 patients succeeded with language test, but only 13 patients succeed with memory test.The difference of success ratios between language test and memory test was significant (P=0.001 ). For memory test, the difference of duration of epilepsy and FIQ in success group and failed group was significantly different (duration of epilepsy : (10.57±4.68) vs (18.30±9.30), P=0.032, FIQ : (81±25.33) vs (64.2±10.86), P=0.046). More grade Ⅱ adverse effects of propofol occured in the patients who failed in memory test (P=0.011 ). Logistic regression results indicated the grade Ⅱ adverse effects of propofol were the main risk factor for memory test failure (OR=28.0, P<0.01). Conclusions Propofol Wada test is an effective method for language dominance evaluation.However, the effect factors for memory dominance evaluation are much more than language evaluation, such as duration of epilepsy, FIQ and grade Ⅱ adverse effects of propofol, and grade Ⅱ adverse effects of propofol may be the most significant risk factor. Key words: Propofol; Wada test; Epilepsy; Language testing; Memory testing

RNA-seq analysis of hippocampal tissues reveals novel candidate genes for drug refractory epilepsy in patients with MTLE-HS

Array-based profiling studies have shown implication of aberrant gene expression patterns in epileptogenesis. We have performed transcriptome analysis of hippocampal tissues resected from patients with MTLE-HS using RNAseq approach. Healthy tissues from tumour margins obtained during tumour surgeries were used as non-epileptic controls. RNA sequencing was performed using standard protocols on Illumina HiSeq 2500 platform. Differential gene expression analysis of the RNAseq data revealed 56 significantly regulated genes in MTLE patients. Gene cluster analysis identified 3 important hubs of genes mostly linked to, neuroinflammation and innate immunity, synaptic transmission and neuronal network modulation which are supportive of intrinsic severity hypothesis of pharmacoresistance. This study identified various genes like FN1 which is central in our analysis, NEUROD6, RELN, TGFβR2, NLRP1, SCRT1, CSNK2B, SCN1B, CABP1, KIF5A and antisense RNAs like AQP4-AS1 and KIRREL3-AS2 providing important insight into the understanding of the pathophysiology or genomic basis of drug refractory epilepsy due to MTS.

A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy.

To evaluate the efficacy and tolerability of the ketogenic diet (KD) during the first 4 months of a randomized controlled trial (RCT) in refractory epilepsy patients aged 1-18 years. Children and adolescents with refractory epilepsy, not eligible for epilepsy surgery, were included. Following 1 month at baseline, patients were randomized to either the KD or to care as usual (CAU).Primary outcome is the proportion of patients with at least 50% reduction in seizure frequency at 4 months. Secondary outcomes are mean percentage of baseline seizures, seizure severity, and side effects. Fifty-seven patients were randomized; nine dropped out, leaving 48 for analysis (i.e., 26 KD, 22 CAU). In an intention-to-treat analysis, 13 patients (50%) treated with the KD and four patients (18.2%) of the CAU group were responders.Mean seizure frequency at 4 months compared to baseline, after removal of two outliers in the KD group, was significantly lower (P = 0.024) in the KD group (56%) (95% CI: 36-76) than in the CAU group (99%) (95% CI: 65-133%).Twice as many patients in the KD group had a relevant decrease in seizure severity score (P = 0.070).Patients treated with the KD had a significantly higher score for gastrointestinal symptoms (P = 0.021) without an increase in the total score of side effects. This trial provides class I evidence that the KD is an effective therapy in children and adolescents with refractory epilepsy compared with CAU. Most often reported side effects are gastrointestinal symptoms.The study has been registered with the Netherlands Trial Registry (NTR2498).

Resecting critical nodes from an epileptogenic circuit in refractory focal-onset epilepsy patients using subtraction ictal SPECT coregistered to MRI.

OBJECTIVE The purpose of this study was to assess the positive predictive value of postresection outcomes obtained by presurgical subtracted ictal SPECT in patients with lesional (MRI positive) and nonlesional (MRI negative) refractory extratemporal lobe epilepsy (ETLE) and temporal lobe epilepsy (TLE). Specifically, outcomes were compared between partial versus complete resection of the regions of transient hyperperfusion identified using subtraction ictal SPECT coregistered to MRI (SISCOM) in relation to the ictal onset zone (IOZ) that was confirmed by electrocorticography (ECoG). That is, SISCOM was used to understand the long-term postsurgical outcomes following resection of the IOZ that overlapped with 1 or more regions of ictal onset-associated transient hyperperfusion. METHODS The study cohort included 44 consecutive patients with refractory ETLE or TLE who were treated between 2002 and 2013 and underwent presurgical evaluation using SISCOM. Concordance was determined between SISCOM localization and the IOZ on the basis of ECoG monitoring. In addition, the association between the extent of the resection site overlapping with the SISCOM signal and postresection outcomes were assessed. Postsurgical follow-up was longer than 24 months in 39 of 44 patients. RESULTS The dominant SISCOM signals were concordant with ECoG and overlapped the resection site in 32 of 44 (73%) patients (19 ETLE and 13 TLE patients), and 20 of 32 (63%) patients became seizure free. In all 19 ETLE patients with concordant SISCOM and ECoG results, the indicated location of ictal onset on ECoG was completely resected; 11 of 19 patients (58%) became seizure free (Engel Class I). In all 13 TLE patients with concordant SISCOM and ECoG results, the indicated ECoG focus was completely resected; 9 of 13 patients (69%) became seizure free (Engel Class I). Complete resection of the SISCOM signal was found in 7 of 34 patients (21%). Of these 7 patients, 5 patients (72%) were seizure free (Engel Class I). Partial resection of the SISCOM signal was found in 16 of 34 patients (47%), and 10 of these 16 patients (63%) were seizure free (Engel Class I) after more than 24 months of follow-up. CONCLUSIONS Concordance between 1 or more SISCOM regions of hyperperfusion with ECoG and at least partial resection of the dominant SISCOM signal in this refractory epilepsy cohort provided additional useful information for predicting long-term postresection outcomes. Such regions are likely critical nodes in more extensive, active, epileptogenic circuits. In addition, SPECT scanner technology may limit the sensitivity of meaningful SISCOM signals for identifying the maximal extent of the localizable epileptogenic network.

Refractory Epilepsy-MRI, EEG and CT scan, a Correlative Clinical Study.

OBJECTIVES:Refractory epilepsies (RE), as well as, the surgically correctable syndromes, are of great interest, since they affect the very young population of children and adolescents. The early diagnosis and treatment are very important in preventing the psychosocial disability. Therefore MRI and EEG are highly sensitive methods in the diagnosis and localization of epileptogenic focus, but also in pre-surgical evaluation of these patients. The aim of our study is to correlate the imaging findings of EEG, MRI and CT scan in refractory symptomatic epilepsies, and to determine their specificity in detecting the epileptogenic focus.METHODS:The study was prospective with duration of over two years, open-labelled, and involved a group of 37 patients that had been evaluated and diagnosed as refractory epilepsy patients. In the evaluation the type and frequency of seizures were considered, together with the etiologic factors and their association, and finally the risk for developing refractory epilepsy was weighted. EEG and MRI findings and CT scan results were evaluated for their specificity and sensitivity in detecting the epileptogenic focus, and the correlation between them was analyzed.RESULTS:Regarding the type of seizures considered in our study, the patients with PCS (partial complex seizures) dominated, as opposed to those with generalized seizures (GS) (D=1.178, p < 0.05). Positive MRI findings were registered in 28 patients (75.7%). Most of them were patients with hippocampal sclerosis, 12 (42.8%), and also they were found to have the highest risk of developing refractory epilepsy (RE) (Odds ratio = 5.7), and the highest association between the etiologic factor and refractory epilepsy (p < 0.01). In detecting the epileptogenic focus, a significant difference was found (p < 0.01) between MRI and CT scan findings, especially in patients with hippocampal sclerosis and cerebral malformations. There was a strong correlation between the MRI findings and the etiologic factor (R = 1), and for CT scan and etiologic factor an R=0.75 correlation. There was a significant difference between imaging methods MRI/CT (p < 0.1), and CT/EEG (p < 0.05) in detecting the etiologic factor, and little difference was noticed between findings of EEG/MRI.CONCLUSION:Our study confirms that for an accurate diagnosis of refractory epilepsy in patients, a combination of neuroimaging and neurophysiologic methods is required. MRI showed to be highly sensitive in detecting the etiologic factor in RE patients, whereas EEG was sensitive in localization of the epileptogenic focus, with high correlation between these two methods. An early diagnosis of these patients is very important in having a better therapeutic response and prognosis for them.

Nuclear Medicine Imaging in Pediatric Neurology.

Nuclear medicine imaging can provide important complementary information in the management of pediatric patients with neurological diseases. Pre-surgical localization of the epileptogenic focus in medically refractory epilepsy patients is the most common indication for nuclear medicine imaging in pediatric neurology. In patients with temporal lobe epilepsy, nuclear medicine imaging is particularly useful when magnetic resonance imaging findings are normal or its findings are discordant with electroencephalogram findings. In pediatric patients with brain tumors, nuclear medicine imaging can be clinically helpful in the diagnosis, directing biopsy, planning therapy, differentiating tumor recurrence from post-treatment sequelae, and assessment of response to therapy. Among other neurological diseases in which nuclear medicine has proved to be useful are patients with head trauma, inflammatory-infectious diseases and hypoxic-ischemic encephalopathy.

A screening tool to identify surgical candidates with drug refractory epilepsy in a resource limited settings

ObjectivesAccess to epilepsy surgery remains a considerable challenge in contemporary healthcare systems. Given the limitations in resources and demand for Epilepsy Monitoring Unit (EMU) assessments, information that can be used to expedite the process is of great value. The purpose of this study was to identify variables prior to EMU admission that may be associated with candidacy for prospective epilepsy surgery. MethodsThis was a prospective study conducted at the Department of Neurology, All India Institute of Medical Sciences, New Delhi, India. We identified two subgroups of patients from 501 drug refractory epilepsy (DRE) patients admitted in EMU of Neurology Department, AIIMS from 2006 onwards following validation of proposed tool in 40 patients. They on subsequent investigations were either cleared or not cleared for epilepsy surgery. A tool consisting of variables likely to predict surgical candidacy in persons with DRE in Indian settings was developed for identification of patients who might benefit from an early epilepsy surgery evaluation. ResultsStatistical analysis revealed significant differences between the two groups for several variables. Non-surgical candidates had non-disabling seizures, seizures improved with a combination of drugs, had little/no AEDs side effects and had near normal or normal scalp EEG and MRI brain. SignificanceUsing the best available evidence, we developed a decision making tool which can provide a comprehensive quick guide for determining candidacy for epilepsy surgery evaluations in resource limited settings. Given the demand for EMU assessments, information that can be used to expedite the process is of value.

The concentration of cell-free DNA in video-EEG patients is dependent on the epilepsy syndrome and duration of epilepsy

Objective: Cell-free DNA (cf-DNA) is a marker of inflammation and cell death. The purpose of the present study was to analyze the role of cf-DNA as a putative biomarker in refractory epilepsy.Methods: Baseline concentration of cf-DNA was measured in the serum of 51 carefully evaluated refractory epilepsy patients undergoing video-EEG monitoring. Epilepsy was classified based on seizure semiology, patient history, and imaging findings. Majority of the patients (47) had focal epilepsy. The association of the concentration cf-DNA with different clinical determinants was analyzed. 250 healthy individuals served as control subjects.Results: The mean baseline concentration of cf-DNA was lower in patients with extra temporal lobe epilepsy (XTLE) compared to control subjects (0.72 μg/ml vs. 0.80 μg/ml; p = 0.001). The difference in concentration of cf-DNA between patients with temporal lobe epilepsy (TLE) and control subjects was not significant. The maximum concentration of cf-DNA after baseline measurement was significantly lower in patients with duration of epilepsy ≥ 18 years compared to those with duration of epilepsy < 18 years (0.022 μg/ml vs. 0.031 μg/ml; p = 0.044). The maximum concentration of cf-DNA was higher in patients with body mass index (BMI) ≥ 25 compared to those with BMI < 25 (0.004 μg/ml vs. 0.041 μg/ml; p = 0.006).Discussion: The difference in cf-DNA concentration between patients with XTLE and control subjects strengthens the previous observations of the importance of epilepsy type with regard of different biomarkers.

RNA-Seq analysis of hippocampal tissues reveals novel candidate genes for drug refractory epilepsy in patients with MTLE-HS

RNA-Seq analysis of hippocampal tissues reveals novel candidate genes for drug refractory epilepsy in patients with MTLE-HS

Topographic congruence of calcified parenchymal neurocysticercosis and other structural brain lesions with epileptiform activity.

Introduction:Calcified parenchymal neurocysticercosis (NCC) lesions are commonly detected in many individuals with refractory epilepsy. However, the relationship between these lesions and epilepsy is not fully determined. We sought to determine if calcified parenchymal NCC demonstrated topographic congruence with epileptiform activity in refractory epilepsy patients. Additional patients with other structural brain lesions were included for comparison.Subjects and Methods:Retrospective cross-sectional analysis of all patients treated at a community-based neurology clinic for refractory epilepsy during a 3-month period and with structural brain lesions detected by neuroimaging studies.Results:A total of 105 patients were included in the study, including 63 with calcified parenchymal NCC lesions and 42 with other structural brain lesions. No significant relationship was detected between hemispheric localization of calcified parenchymal NCC lesions and epileptiform activity. For those with other structural brain lesions, the hemispheric localization was significantly related to the side of epileptiform activity (Chi-square = 11.13, P = 0.025). In addition, logistic regression models showed that those with right-sided non-NCC lesions were more likely to have right-sided epileptiform activity (odds ratio = 4.36, 95% confidence interval [CI] =1.16–16.31, P = 0.029), and those with left-sided non-NCC lesions were more likely to have left-sided epileptiform activity (odds ratio = 7.60, 95% CI = 1.89–30.49, P = 0.004).Conclusion:The lack of correlation between the side of calcified parenchymal NCC lesions and the side of the epileptiform activity suggests that these lesions may be incidental findings in many patients.

Long-Term Outcome of Vagus Nerve Stimulation Therapy in Young Children with Intractable Epilepsy

Vagus nerve stimulation (VNS) is approved by FDA for treatment of intractable epilepsy in children over 12 years of age. We assessed the efficacy of VNS therapy in younger children. The study was a retrospective review of the medical records of medically refractory epilepsy patients under 12 years old at VNS implantation. Out of 42 patients studied, 28 had at least 50% decrease in seizure frequency, one-half of patients had 75% decrease in seizures, and 7% became seizure-free. A total 69% of patients reported improved mood and alertness. Complication rate was 7%. Age at VNS implantation, prior duration of epilepsy, electroencelphographic focality, and etiology of epilepsy did not influence the outcome ( p > 0.05). Our cohort demonstrated a lasting benefit of VNS therapy over 5 years, including seizure reduction and improved mood and alertness. VNS is a safe and effective adjunctive therapy for young children with medically intractable epilepsy.

Surgical management of medically refractory epilepsy in patients with polymicrogyria.

Polymicrogyria (PMG) is a malformation of cortical development characterized by formation of an excessive number of small gyri. Sixty percent to 85% of patients with PMG have epilepsy that is refractory to medication, but surgical options are usually limited. We characterize a cohort of patient with polymicrogyria who underwent epilepsy surgery and document seizure outcomes. A retrospective study of all patients with PMG who underwent epilepsy surgery (focal seizure foci resection and/or hemispherectomy) at our center was performed by review of all clinical data related to their treatment. We identified 12 patients (7 males and 5 female) with mean age of 18 (ranging from 3 months to 44 years) at time of surgery. Mean age at seizure onset was 8 years, with the majority (83%) having childhood onset. Six patients had focal, five had multifocal, and one patient had diffuse PMG. Perisylvian PMG was the most common pattern seen on magnetic resonance imaging (MRI). Eight patients had other cortical malformations including hemimegalencephaly and cortical dysplasia. Scalp electroencephalography (EEG) often showed diffuse epileptic discharges that poorly lateralized but were focal on intracranial electrocorticography (ECoG). Eight patients underwent seizure foci resection and four underwent hemispherectomy. Mean follow-up was 7 years (ranging from one to 19 years). Six patients (50%) were seizure-free at last follow-up. One patient had rare seizures (Engel class II). Three patients were Engel class III, having either decreased seizure frequency or severity, and two patients were Engel class IV. Gross total resection of the PMG cortex trended toward good seizure control. Our study shows that even in patients with extensive or bilateral PMG malformations, some may still be good candidates for surgery because the epileptogenic zone may involve only a portion of the malformation. Intracranial ECoG can provide additional localizing information compared to scalp EEG in guiding resection of epileptogenic foci.

Serum MicroRNA-4521 is a Potential Biomarker for Focal Cortical Dysplasia with Refractory Epilepsy.

Early biomarker-based diagnosis of focal cortical dysplasia (FCD) represents a major clinical challenge. The aim of this study was to identify novel brain microRNAs (miRNAs) in patients with refractory epilepsy and FCD as potential biomarkers. We evaluated serum hsa-miR-4521 as a promising novel biomarker in patients with FCD. Tissue for microarray was obtained from nine patients with temporal lobe refractory epilepsy who underwent surgery to remove epileptic foci identified by cortical video electroencephalogram monitoring. Control tissue was collected from eight patients with hypertension who required emergency surgery to remove an intracranial hematoma. The Affymetrix® GeneChip® Command Console® Software (Affymetrix miRNA 4.0) was used to compare miRNA expression in the cerebral cortex of experimental and control patients. Temporal cortex tissue and serum samples were taken from the same patients for verification of hsa-miR-4521 expression by real-time quantitative polymerase chain reaction (RT-qPCR). The experimental and control patients did not differ significantly in terms of age and gender. 19.4 % (148/764) of the total miRNAs were differentially expressed in experimental and control tissue, which is in agreement with the existing literature. We selected miRNA-4521 for further analysis; the fold-change in expression was 14.4707 and the q value was almost 0, which confirmed up-regulation. Significant up-regulation of hsa-miR-4521 was further validated by RT-qPCR. miRNA microarrays can efficiently and conveniently identify differentially expressed miRNAs in epilepsy brain tissue. This is the first study to identify differential expression of hsa-miR-4521 in brain tissue and serum of refractory epilepsy patients and suggests that serum hsa-miR-4521 may represent a potential diagnostic biomarker for FCD with refractory epilepsy.

Perfusion SPECT, SISCOM and PET (18)F-FDG in the assessment of drug- refractory epilepsy patients candidates for epilepsy surgery.

Brain perfusion SPECT (ictal-interictal), SPECT images and subtraction ictal SPECT coregistered to MRI (SISCOM) and (18)F-FDG-PET (interictal), play an important role in the pre-surgical diagnosis of patients with medically refractory epilepsy. This study aimed to establish: the reproducibility of visual ictal-interictal SPECT and SISCOM analysis altogether with the capacity of SPECT, SISCOM and PET to determine the epileptogenic zone. (99m)Tc-HMPAO SPECT ictal-interictal and SISCOM (Analyze 7.0) were performed on 47 refractory epilepsy patients (24 F, 19-60 yrs). In 13 patients, SISCOM was also performed using a new program (Focus DET). Ictal-interictal SPECT and SISCOM images were analysed independently by two nuclear medicine physicians (observer 1 and 2). Kappa concordance coefficient was used to evaluate the reproducibility. In sixteen patients, SPECT, SISCOM and PET findings were compared with the resected area during the surgery, and surgical outcome using Engel scale or with the stereo EEG-(SEEG). The ictal-interictal SPECT interobserver agreement was 91%, Kappa index 0.86, SISCOM (Analyze 7.0) interobserver agreement percentage was 82%, Kappa index 0.80, Analyze 7.0 showed a higher inconclusive results than visual SPECT analysis. SISCOM FocusDET interobserver agreement was 92%, Kappa index 0.87, with lower inconclusive results than Analyze 7.0. SPECT, SISCOM and PET combined findings identified 87% seizure onset zone: 79% temporal, 26% parieto-temporal and 7% frontal. Ictal-interictal SPECT and SISCOM showed a high reproducibility in this sample of patients with drug-refractory epilepsy. SPECT,SISCOM and PET combined findings improved detection of epileptogenic zone in comparison with the individual assessment.

Perfusion SPECT, SISCOM and PET 18F-FDG in the assessment of drug-refractory epilepsy patients candidates for epilepsy surgery

AimsBrain perfusion SPECT (ictal–interictal), SPECT images and subtraction ictal SPECT coregistered to MRI (SISCOM) and 18F-FDG-PET (interictal) play an important role in the pre-surgical diagnosis of patients with medically refractory epilepsy.This study aimed to establish the reproducibility of visual ictal–interictal SPECT and SISCOM analysis altogether with the capacity of SPECT, SISCOM and PET to determine the epileptogenic zone. Material and methods99mTc-HMPAO SPECT ictal–interictal and SISCOM (Analyze 7.0) were performed on 47 refractory epilepsy patients (24 F, 19–60 yrs). In 13 patients, SISCOM was also performed using a new programme (Focus DET). Ictal–interictal SPECT and SISCOM images were analyzed independently by two nuclear medicine physicians (observers 1 and 2). Kappa concordance coefficient was used to evaluate the reproducibility. In sixteen patients, SPECT, SISCOM and PET findings were compared with the resected area during the surgery, and surgical outcome using Engel scale or with the stereo EEG-(SEEG). ResultsThe ictal–interictal SPECT interobserver agreement was 91%, Kappa index 0.86, SISCOM (Analyze 7.0) interobserver agreement percentage was 82%, Kappa index 0.80, Analyze 7.0 showed a higher inconclusive results than visual SPECT analysis. SISCOM FocusDET interobserver agreement was 92%, Kappa index 0.87, with lower inconclusive results than Analyze 7.0. SPECT, SISCOM and PET combined findings identified 87% seizure onset zone: 79% temporal, 26% parieto-temporal and 7% frontal. ConclusionsIctal–interictal SPECT and SISCOM showed a high reproducibility in this sample of patients with drug-refractory epilepsy. SPECT, SISCOM and PET combined findings improved detection of epileptogenic zone in comparison with the individual assessment.

Connectome Reorganization Associated With Surgical Outcome in Temporal Lobe Epilepsy.

To identify the distinct pattern of anatomical network reorganization in surgically refractory mesial temporal lobe epilepsy (MTLE) patients using a longitudinal design. We collected longitudinal diffusion-weighted images of 19 MTLE patients before and after anterior temporal lobectomy. Patients were classified as seizure-free (SF) or nonseizure-free (NSF) at least 1 year after surgery. We constructed whole-brain anatomical networks derived from white matter tractography and evaluated network connectivity measures by graph theoretical analysis. The reorganization trajectories of network measures in SF and NSF patients were investigated by two-way mixed analysis of variance, with factors "group" (SF vs NSF) and "treatment" (presurgery vs postsurgery). Widespread brain structures showed opposite reorganization trajectories in FS and NSF groups (interaction effect). Most of them showed group difference before surgery and then converge after surgery, suggesting that surgery remodeled these structures into a similar status. Conversly, contralateral amygdala-planum-temporale and thalamic-parietal tracts showed higher connectivity strength in NSF than in SF patients after surgery, indicating maladaptive neuroplastic responses to surgery in NSF patients. Our findings suggest that surgical outcomes are associated not only with the preoperative pattern of anatomical connectivity, but also with connectome reconfiguration following surgery. The reorganization of contralateral temporal lobe and corticothalamic tracts may be particularly important for seizure control in MTLE.

A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation

PurposeThis study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). MethodsThirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. ResultsSixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35bpm heart rate increase, minimum of 100bpm). Multiple CBSDA settings achieved a sensitivity of ≥80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ±2min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials. ConclusionsThe investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients.