Low‐frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy: A controlled clinical study

Purpose: This study was designed to evaluate the therapeutic effect of low‐frequency repetitive transcranial magnetic stimulation (rTMS) on patients with refractory partial epilepsy. Methods: Sixty‐four patients with refractory focal epilepsy were screened and 60 patients were randomly divided into two groups by stimulation intensity: 90% (group 1) or 20% (group 2) of resting motor threshold (rMT). Seizure frequency and interictal EEG epileptic discharges were compared between the baseline and follow‐up periods. Key Findings: Seizures significantly decreased following 2‐weeks high intensity (90% rMT) rTMS treatment compared with baseline level (p < 0.05). rTMS also decreased interictal epilepsy discharges and improved the scales of Symptom Checklist‐90 significantly (p < 0.05). Seizures and spikes in the follow‐up period in the patients who received low intensity (20% rMT) rTMS did not show any difference compared with baseline data (p > 0.05, respectively). Significance: Low‐frequency high intensity rTMS (90% rMT) delivered into the epileptogenic zone had a significant antiepileptic effect on patients with refractory partial seizures. rTMS treatment can also reduce the interictal epileptic discharge frequency and improve the psychological condition of these patients.     

Low-frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy-a pilot study.

We evaluated the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure frequency in adult patients with medically intractable extratemporal lobe epilepsy (ETLE). Seven patients with medically intractable ETLE received low-frequency rTMS at 0.9 Hz, basically two sets of 15 min stimulation per day for five days in a week, with the stimulus intensity of 90% of resting motor threshold (RMT). The number of seizures during two weeks before and after the stimulation of one week was compared. Furthermore, RMT and active motor threshold (AMT) were measured before and after rTMS for each daily session. After low-frequency rTMS of one week, the frequency of all seizure types, complex partial seizures (CPSs) and simple partial seizures was reduced by 19.1, 35.9 and 7.4%, respectively. The patients with smaller difference between RMT and AMT before rTMS had higher reduction rate of CPSs. A favorable tendency of seizure reduction, though not statistically significant, during two weeks after low-frequency rTMS was demonstrated in medically intractable ETLE patients. As far as CPSs are concerned, smaller decrease of motor threshold by voluntary muscle contraction was associated with better response to rTMS.     

The Absence of Interictal Spikes with Documented Seizures Suggests Extratemporal Epilepsy

PURPOSE: To determine the demographic and clinical characteristics of patients who have documented epileptic seizures on long-term video-EEG monitoring who do not have interictal spikes. METHODS: The records of 1,223 monitoring studies from 919 patients who underwent noninvasive long-term video-EEG monitoring were reviewed. In 28 patients (3.0% of monitored patients, 4.4% of patients with electrographic evidence of epilepsy), no interictal spikes were found despite the occurrence of at least one recorded electrographic seizure. The demographic, medical, neuropsychological, and EEG data of these patients were compared with those of 28 matched control patients with documented interictal spikes. RESULTS: Extratemporal seizures were significantly more frequent in the patients with at least one recorded epileptic seizure but without interictal spikes compared with patients with epileptic seizures and interictal spikes (p = 0.031). The only other significant difference between the groups (p = 0.016) was a later age at seizure onset (18.3 vs. 10.7 years) for the patients without interictal spikes. Age at evaluation, gender, handedness, clinical seizure type, family history of epilepsy, history of febrile seizures, neuropsychological testing, and neurologic and psychiatric history did not differ between the two groups. CONCLUSIONS: In patients with documented epilepsy without interictal spikes on EEG monitoring, the possibility of an extratemporal focus should be considered.     

Antiepileptic effects of low frequency repetitive transcranial magnetic stimulation: A meta-analysis

Purpose

To evaluate the antiepileptic efficacy of low frequency repetitive transcranial magnetic stimulation (rTMS) in medically intractable epilepsy.

Methods

A comprehensive literature search was performed on articles published from 1990 to 2010 in Medline, Pubmed, CINAHL, and Cochrane using the following keywords: epilepsy, seizure, transcranial magnetic stimulation, repetitive transcranial magnetic stimulation. Two reviewers assessed article eligibility and extracted the data independently. For outcome measures, effect size and 95% confidence interval (CI) were calculated for seizure frequency, spike number, duration of epileptiform abnormalities (EAs), and resting motor threshold (RMT) by using fixed and random effect models.

Results

Eleven articles were identified, with a total of 164 participants. Based on seizure frequency, a significant effect size was found (effect size: 0.34, with a 95% CI at 0.10–0.57). Considering between-study heterogeneity, we conducted a second meta-analysis, and the underlying etiology was considered important for the treatment effect. Cortical dysplasia or neocortical epilepsy showed an effect size of 0.71, with a 95% CI at 0.30–1.12. In contrast, other epileptic disorders showed an effect size of 0.22.

Conclusion

Low frequency rTMS has a favorable effect on seizure reduction, particularly evident in patients with neocortical epilepsy or cortical dysplasia.     

Effects of low-frequency repetitive transcranial magnetic stimulation on electroencephalogram and seizure frequency in 15 patients with temporal lobe epilepsy following dipole source localization

BACKGROUND:Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to significantly reduce epileptiform discharges and control clinical seizures in intractable epilepsy patients. The location of epileptic foci and magnetic stimulation sites remain uncertain. The effects of rTMS on electroencephalogram and seizure remain unclear in epileptic patients following dipole source localization. OBJECTIVE: To investigate the effects of low-frequency rTMS on electroencephalogram and seizure i...     

A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy

OBJECTIVE: To study the antiepileptic effects of rTMS in patients with refractory epilepsy and malformations of cortical development in a randomized, double-blind, sham-controlled trial. METHODS: Twenty-one patients with malformations of cortical development and refractory epilepsy underwent five consecutive sessions of low-frequency rTMS, either sham or active (1Hz, 1,200 pulses), focally targeting the malformations of cortical development. The number of epileptiform discharges in the electroencephalogram and the number of clinical seizures were measured before (baseline), immediately after, as well as 30 and 60 days after rTMS treatment. RESULTS: rTMS significantly decreased the number of seizures in the active compared with sham rTMS group (p < 0.0001), and this effect lasted for at least 2 months. Furthermore, there was a significant decrease in the number of epileptiform discharges immediately after (p = 0.01) and at week 4 (p = 0.03) in the active rTMS group only. There were few mild adverse effects equally distributed in both groups. The preliminary cognitive evaluation suggests improvement in some aspects of cognition in the active rTMS group only. INTERPRETATION: Noninvasive brain stimulation for epilepsy may be an alternative treatment for pharmaco-resistant patients with clearly identifiable seizure foci in the cortical convexity and who are not eligible for surgical treatment.     

Subacute electrical stimulation of the hippocampus blocks intractable temporal lobe seizures and paroxysmal EEG activities

PURPOSE: To investigate the clinical, electroencephalographic (EEG), and histopathologic effects of subacute electrical stimulation of the hippocampal formation or gyrus (SAHCS) on 10 patients with intractable temporal lobe seizures. METHODS: Bilateral, depth, hippocampal or unilateral, subdural, basotemporal electrodes were implanted in all 10 patients for a topographic diagnosis of the site and extent of the epileptic focus before a temporal lobectomy. In all patients, antiepileptic drugs (AEDs) were discontinued from 48 to 72 h before a program of continuous SAHCS, which was performed for 2-3 weeks. Stimulation parameters were biphasic Lilly wave pulses, 130/s in frequency, 450 micros in duration, and 200-400 microA in amplitude. The stimuli were delivered 23 of every 24 h for the 2-3-week SAHCS period. The effects of SAHCS on the number of clinical seizures per day and the percentage of interictal EEG spikes per 10-second samples of maximal paroxysmal activity at the epileptic focus were determined daily during the 16 days of SAHCS. At the completion of this program, patients underwent an en bloc temporal lobectomy, and the histopathologic effects of SAHCS on the stimulated tissue were analyzed by means of light-microscopy studies. RESULTS: In seven patients whose stimulation electrode contacts were placed within the hippocampal formation or gyrus and who experienced no interruption in the stimulation program, SAHCS abolished clinical seizures and significantly decreased the number of interictal EEG spikes at the focus after 5-6 days. The most evident and fast responses were found by stimulating either the anterior pes hippocampus close to the amygdala or the anterior parahippocampal gyrus close to the entorhinal cortex. Other surface, hippocampal, and basotemporal EEG signs predicted and accompanied this antiepileptic response. These included an electropositive DC shift and monomorphic delta activity at the medial hippocampal and parahippocampal regions, and a normalization of the background EEG activity and signs of slow-wave sleep in surface. depth, and subdural regions. In contrast, no evident antiepileptic responses or no responses at all were found in three patients when stimulation was either interrupted or when it was administered outside the hippocampus. Light microscopy analysis of the stimulated hippocampal tissue showed histopathological abnormalities attributable to the depth-electrode penetration damage or to the pial surface reaction to the subdural, Silastic electrode plate. However, no evident histopathological differences were found between the stimulated and nonstimulated hippocampal tissue. CONCLUSIONS: SAHCS appears to be a safe procedure that can suppress temporal lobe epileptogenesis with no additional damage to the stimulated tissue.     

低频重复经颅磁刺激对难治性癫发作频率、静息运动阈值、SPECT的影响

目的：观察低频重复经颅磁刺激（rTMS）的抗癫疗效及可能机制。方法：对4例难治性癫患者灶所在脑区给予rTMS治疗（0.5 Hz,45%最大输出强度,每天15串、100次/串、串间隔30 s,连续10 d）,观察治疗前后各3个月患者的临床发作及1 h时长的脑电图癫波数量,并行单光子发射断层摄影（SPECT）和静息运动阈值检查,以观察感兴趣区（ROI）放射线摄取比值的变化和皮质兴奋性改变。结果：4例患者经rTMS治疗后,3例无发作,1例发作1次。脑电图：1例癫波减少了20%;4例静息运动阈值均增高。SPECT：4例均显示rTMS后ROI值进一步降低。结论：低频rTMS对难治性癫有治疗作用,其抗癫作用可能与减少癫灶局部脑血流灌注和增加静息运动阈值有关。     

High-frequency (80-500 Hz) oscillations and epileptogenesis in temporal lobe epilepsy

High-frequency oscillations (HFOs), termed ripples (80-200 Hz) and fast ripples (250-600 Hz), are recorded in the EEG of epileptic patients and in animal epilepsy models; HFOs are thought to reflect pathological activity and seizure onset zones. Here, we analyzed the temporal and spatial evolution of interictal spikes with and without HFOs in the rat pilocarpine model of temporal lobe epilepsy. Depth electrode recordings from dentate gyrus (DG), CA3 region, subiculum and entorhinal cortex (EC), were obtained from rats between the 4th and 15th day after a status epilepticus (SE) induced by i.p. injection of pilocarpine. The first seizure occurred 6.1 ± 2.5 days after SE (n = 7 rats). Five of 7 animals exhibited interictal spikes that co-occurred with fast ripples accounting for 4.9 ± 4.6% of all analyzed interictal spikes (n = 12,886) while all rats showed interictal spikes co-occurring with ripples, accounting for 14.3 ± 3.4% of all events. Increased rates of interictal spikes without HFOs in the EC predicted upcoming seizures on the following day, while rates of interictal spikes with fast ripples in CA3 reflected periods of high seizure occurrence. Finally, interictal spikes co-occurring with ripples did not show any specific relation to seizure occurrence. Our findings identify different temporal and spatial developmental patterns for the rates of interictal spikes with or without HFOs in relation with seizure occurrence. These distinct categories of interictal spikes point at dynamic processes that should bring neuronal networks close to seizure generation.     

In-session seizures during low-frequency repetitive transcranial magnetic stimulation in patients with epilepsy

Low-frequency repetitive transcranial magnetic stimulation (rTMS) is emerging as a therapeutic tool for patients with intractable epilepsy. Although seizures during treatment have been reported as adverse events in some patients, the nature and severity of seizures that may be provoked by low-frequency rTMS in patients with epilepsy have not been extensively studied. Accordingly, this article documents seizures in patients (n = 5) with intractable epilepsy and average seizure frequency greater than one per day who underwent 1-Hz rTMS for seizure suppression. We report three observations in the present case series: (1) in each instance the in-session seizure was typical in semiology to the patient’s habitual seizures, (2) the duration of each documented seizure was either the same as or shorter than the patients’ baseline seizures, and (3) the overall neurological outcome on follow-up was not affected by the in-session seizures. More data will be required for valid conclusions with respect to safety and tolerability of low-frequency rTMS in patients with epilepsy, but it is noteworthy from our perspective that seizures during rTMS in this series were similar to the patients’ habitual seizures, occurred in patients with epilepsy with baseline seizure frequency exceeding one per day, and did not correlate with a poor neurological outcome or with absence of clinical response to rTMS.     

Experimental therapy of epilepsy with transcranial magnetic stimulation: lack of additional benefit with prolonged treatment

OBJECTIVE: To investigate the effect of three months of low-frequency repetitive transcranial magnetic stimulation (rTMS) treatment in intractable epilepsy. METHODS: Five patients (four males, one female; ages 6 to 50 years), were enrolled in the study; their epilepsy could not be controlled by medical treatment and surgery was not indicated. rTMS was performed twice a week for three months; patients kept records of seizure frequency for an equal period of time before, during, and after rTMS sessions. rTMS was delivered to the vertex with a round coil, at an intensity 5% below motor threshold. During rTMS sessions, 100 stimuli (five series of 20 stimuli, with one-minute intervals between series) were delivered at a frequency of 0.3 Hz. RESULTS: Mean daily number of seizures (MDNS) decreased in three patients and increased in two during rTMS--one of these was treated for only one month; the best result was achieved in a patient with focal cortical dysplasia (reduction of 43.09% in MDNS). In the whole patient group, there was a significant (p<0.01) decrease in MDNS of 22.8%. CONCLUSION: Although prolonged rTMS treatment is safe and moderately decreases MDNS in a group of patients with intractable epilepsy, individual patient responses were mostly subtle and clinical relevance of this method is probably low. Our data suggest, however, that patients with focal cortical lesions may indeed benefit from this novel treatment. Further studies should concentrate on that patient subgroup.     

Cortical resection with electrocorticography for intractable porencephaly-related partial epilepsy

PURPOSE: We evaluated the results of cortical resection of epileptogenic tissue for treatment of intractable porencephaly-related epilepsy. METHODS: We examined clinical features, electrophysiological data, surgical findings, and seizure outcomes after cortical resection in eight patients with intractable epilepsy related to porencephalic cysts. RESULTS: All eight patients had hemiparesis. Five retained motor function in the hemiparetic extremities; six retained visual fields. All had partial seizures, six with secondary generalization. Seven patients had simple and three had complex partial seizures (CPSs); two also had drop attacks. Four patients had multiple seizure types. Long-term scalp video-EEG (LVEEG) localized interictal epileptic abnormalities that anatomically corresponded to the cyst location in three patients. LVEEG recorded ictal-onset zones in five; these anatomically corresponded to the cyst location in three of the five. EEG recorded generalized seizures in two patients, hemispheric in one, and multifocal in two. Intraoperative electrocorticography (ECoG) revealed interictal epileptic areas extending beyond the margins of the cyst in seven patients. We resected ECoG-localized interictal epileptic areas completely in five patients and partially in two. Cortical resection was based on seizure semiology and LVEEG in one patient whose ECoG showed no epileptiform discharges. After a minimum follow-up of 1 year, six patients had excellent seizure outcome (Engel class I), and two had a >90% seizure reduction (Engel class III) without complications. CONCLUSIONS: Cortical resection guided by ECoG allows preservation of motor function and visual field and provides an effective surgical procedure for treatment of intractable epilepsy secondary to porencephaly.     

立体定向毁损杏仁海马复合体治疗癫痫长期随访

目的 探讨立体定向射频毁损杏仁海马复合体，能否阻止癫痫放电的传播以治疗顽固性癫痫。方法 17例顽固性癫痫病人应用ZD立体定向系统，CT扫描确定杏仁核和海马的靶点，分别毁损杏仁核和海马。术后常规MR复查了解靶点毁损的部位和大小，并排除并发症。结果 本组17例，无手术并发症。随访2～6年，平均3年9个月，结果满意者7例(癫痫发作消失)，显著改善者7例(癫痫发作减少75％)，无效者1例，1例自行停药2月后，癫痫发作又复发，再次服药后仍有癫痫发作。所有患者均需服药，药量无明显减少。结论 立体定向射频毁损杏仁海马复合体治疗癫痫，创伤小，安全，控制癫痫发作基本满意，长期有效。     

Characteristics of dipoles in clustered individual spikes and averaged spikes

The aim of this study is to analyze the characteristics of dipoles in clustered individual spikes and averaged spikes, we compared electroencephalography (EEG) dipole localizations from patients with intractable extratemporal lobe epilepsy (IETLE) and from patients with benign epilepsy with centrotemporal spikes (BECTS).We studied 10 patients; five with IETLE who underwent epilepsy surgery after subdural EEG and five with BECTS. We recorded 19-channel digital scalp EEGs and used clustering analysis for individual spikes to characterize interictal spikes. We selected and averaged one representative spike group at the maximum negative peak electrode. We used a single dipole method with three-shell spherical head model. We compared dipole localizations of both averaged and individual spikes.IETLE data had more identifiable spike clusters and fewer spikes in each cluster than BECTS (P<0.05). Dipole sources with goodness-of-fit >or=95% in averaged spikes were less frequent in IETLE than in BECTS (P<0.05). For IETLE, averaged spikes showed no dipoles (two patients), while individual spikes gave dipole sources reliably in the epileptic region. For BECTS, individual and averaged spike sources were clustered. More than 80% of dipoles in averaged spikes were stable, in close proximity, for prolonged periods in BECTS.More spike groups after clustering and fewer acceptable dipoles from averaged spikes in IETLE reflect variable spike activity over extensive epileptic regions. Fewer spike groups producing more acceptable dipoles in BECTS correlate with stable spike sources within the isolated epileptic central region. Characteristics of clustered interictal spikes need careful examination before the use of dipole analysis of averaged spikes for epilepsy evaluation.     

Localizing value of alpha-methyl-L-tryptophan PET in intractable epilepsy of neocortical origin.

BACKGROUND: [(11)C] alpha-methyl-L-tryptophan (alpha-MTrp) has been developed as a tracer for the study of the synthesis of serotonin in the brain with PET. However, it has been shown that in pathologic conditions the tracer may reflect the activation of kynurenine metabolism. Increased levels of serotonin and quinolinic acid have been described in resected epileptogenic cortex, raising the possibility that alpha-MTrp can localize seizure foci in patients with intractable partial epilepsy. The authors assessed the uptake of alpha-MTrp in 18 patients (11 men, mean +/- SD age 27.1 +/- 10.1 years, range 13 to 54) with intractable partial epilepsy to correlate the PET findings with the epileptogenic area defined by electroclinical and neuroimaging data. METHOD: Seven patients with cortical dysplasia (CD) and 11 with partial epilepsy in which conventional MRI and fluorine-18-deoxyglucose ((18)FDG)-PET studies failed to detect any abnormality were studied. All underwent scalp EEG monitoring during the PET scan to exclude ictal events and estimate the interictal epileptic activity. RESULTS: In seven patients (39%; CD four and cryptogenic partial epilepsy three), PET showed focal increased uptake of alpha-MTrp corresponding to the epileptogenic area. alpha-MTrp uptake in the epileptic focus correlated with the frequency of interictal spikes (r = 0.7, p < 0.05). CONCLUSIONS: alpha-MTrp-PET may be of value in the localization of the epileptogenic area not only in patients with visible dysplastic lesions, but also in those with cryptogenic partial epilepsy.     

Current trends in electroencephalography

Several recent articles re-emphasize the value of clinical electrophysiology: in localizing epileptogenesis, predicting effectiveness of epilepsy surgery, and disclosing a mechanism of benign Rolandic epilepsy of childhood.A review of the role of EEG in the diagnosis of epilepsy indicated that epileptiform activity will appear in 50% of initial awake recordings of adults with epilepsy and in 85% of subjects undergoing two recordings. This contrasts with the appearance of spikes in only 4 of 1000 normal persons. Several studies focused on the value of electroencephalography in extratemporal epilepsy: 62% of patients with neocortical epilepsy had at least one localizing ictal EEG; occipital and temporal neocortical seizures were localized in a greater proportion than frontal or parietal attacks. Interictal spikes, if unifocal, always arose from the epileptogenic region in a study of their seizure localizing value. Such congruence augured for better seizure control by focal resection in two studies reviewed herein.Studies indicating the value of interictal temporal lobe spikes and scalp-recorded seizures in lateralising a temporal seizure focus are reviewed. One study found EEG to be slightly more reliable for lateralization of temporal epileptogenesis than MRI.In patients with benign Rolandic seizures, enhanced motor evoked potentials (MEPs) were obtained from transcranial magnetic stimulation when this was applied 50-80 msec after electrical stimulation of the thumb whereas this interval inhibited the MEP in normal subjects. This suggests that afferent cutaneous input abnormally and synchronously activates a large population of sensory neurons; such activation is subsequently transmitted to the motor cortex to produce the focal spikes in this condition.Finally, advances in non-invasive technology have redefined and limited the need for invasive monitoring in children with intractable seizure disorders.     

Slow repetitive TMS for drug-resistant epilepsy: clinical and EEG findings of a placebo-controlled trial

PURPOSE: To assess the effectiveness of slow repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for drug-resistant epilepsy. METHODS: Forty-three patients with drug-resistant epilepsy from eight Italian Centers underwent a randomized, double-blind, sham-controlled, crossover study on the clinical and EEG effects of slow rTMS. The stimulus frequency was 0.3 Hz. One thousand stimuli per day were given at the resting motor threshold intensity for 5 consecutive days, with a round coil at the vertex. RESULTS: "Active" rTMS was no better than placebo for seizure reduction. However, it decreased interictal EEG epileptiform abnormalities significantly (p < 0.05) in one-third of the patients, which supports a detectable biologic effect. No correlation linked the rTMS effects on seizure frequency to syndrome or anatomic classification, seizure type, EEG changes, or resting motor threshold (an index of motor cortex excitability). CONCLUSIONS: Although the antiepileptic action was not significant (p > 0.05), the individual EEG reactivity to "active" rTMS may be encouraging for the development of more-powerful, noninvasive neuromodulatory strategies.     

Mutually suppressive interrelations of symmetric epileptic foci in bitemporal epilepsy and their inhibitory stimulation

OBJECTIVES: The goal of this study is to analyze the suppressive interaction of symmetric temporal lobe epileptic foci, assess some failures of epilepsy surgery, and evaluate the possibility of terminating focal seizures with stimulation of symmetric epileptic foci. MATERIALS AND METHODS: One hundred and twenty-nine intractable epilepsy patients (age range 6-53 years) with bitemporal epileptiform abnormalities in multiple scalp EEGs were evaluated with chronically implanted depth and subdural electrodes. Interelectrode coherence and power spectra were studied using internally developed software. RESULTS: Bitemporal epileptic foci were found in 85/129 (66%) patients with reciprocal relations between these foci in 57/85 (67%) patients. Temporal lobectomy was performed for 67/85 patients. 12/67 patients became free of seizures (Engel's Class I), 32/67 improved (Classes II and III), and 23/67 did not improve. 14/23 patients demonstrated post-surgical activation of the contralateral temporal lobe epileptic focus. For 8/14 of these patients, the stereotactic cryoamygdalatomy was performed in the temporal lobe contralateral to the first surgery. 5/8 patients became free of seizures. It was found that stimulation of temporal lobe deep epileptic focus may terminate focal seizures in the contralateral symmetric structures. CONCLUSION: A mutually suppressive relationship is one of variants of the interaction of symmetric epileptic foci. Some epilepsy surgery failures may be a result of post-surgical activation of the intact focus. The increase of coherence between both temporal lobes before the seizure onset of the seizure suggests the establishment of functional interrelations between two epileptic foci at an early, "hidden" phase of seizures, and may predict the direction of seizure spread. Mutually suppressive interrelations of symmetric epileptic foci might be employed for chronic therapeutic stimulation.     

Effects of amygdala-hippocampal stimulation on interictal epileptic discharges

Deep brain stimulation (DBS) of different nuclei is being evaluated as a treatment for epilepsy. While encouraging results have been reported, the effects of changes in stimulation parameters have been poorly studied. Here the effects of changes of pulse waveform in high frequency DBS (130 Hz) of the amygdala-hippocampal complex (AH) are presented. These effects were studied on interictal epileptic discharge rates (IEDRs). AH-DBS was implemented with biphasic versus pseudo monophasic charge balanced pulses, in two groups of patients: six with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) and six with non lesional (NLES) temporal epilepsy. In patients with HS, IEDRs were significantly reduced with AH-DBS applied with biphasic pulses in comparison with monophasic pulse. IEDRs were significantly reduced in only two patients with NLES independently to stimulus waveform. Comparison to long-term seizure outcome suggests that IEDRs could be used as a neurophysiological marker of chronic AH-DBS and they suggest that the waveform of the electrical stimuli can play a major role in DBS. We concluded that biphasic stimuli are more efficient than pseudo monophasic pulses in AH-DBS in patients with HS. In patients with NLES epilepsy, other parameters relevant for efficacy of DBS remain to be determined.     

Changes of EEG synchronization during low-frequency electric stimulation of the seizure onset zone

PURPOSE: To assess whether EEG synchronization changes during short-term low-frequency electrical stimulation of the seizure onset zone. METHODS: In 10 patients (34+/-11 years) with pharmaco-resistant epilepsy the seizure onset zone (9 temporal lobe, 1 frontal lobe) was electrically stimulated at 1Hz for 5min via intracranial electrodes. Bipolar stimuli were applied and four pulse widths (0.05, 0.1, 0.5, and 1.0ms) were tested. Stimulation amplitudes were held fixed at 1mA for strip electrodes and at 2mA for depth electrodes. Changes of EEG synchronization were assessed by the eigenvalue dynamics of the cross-correlation matrix computed from a 2.5s sliding window. RESULTS: 37 stimulations were performed. We observed EEG desynchronization in 49% (18/37), an increase of EEG synchronization in 27% (10/37) and an EEG pattern with no significant change of synchronization in 24% (9/37). EEG synchronization most frequently occurred when stimulating with a pulse width of 0.5ms. In a patient with bilateral independent seizure onsets stimulation effects on EEG synchronization were different for each side. In the patient with the shortest duration of temporal lobe epilepsy, stimulation triggered periodic epileptic spikes phase-locked to stimulation. One patient experienced an aura during stimulation, which did not evolve into a seizure, and in one patient a sub-clincial seizure occurred. DISCUSSION: Low-frequency stimulation of the seizure onset zone is associated with different changes of EEG synchronization and its effects depend on the widths of the stimulation pulses. It may be an appropriate stimulation technique for long-term studies assessing whether synchronized or desynchronized brain dynamics prevent seizure occurrence.