Spike persistence and normalization in benign epilepsy with centrotemporal spikes – Implications for management

Purpose

This study was performed 1) to determine the timing of spike normalization in patients with benign epilepsy with centrotemporal spikes (BECTS); 2) to identify relationships between age of seizure onset, age of spike normalization, years of spike persistence and treatment; and 3) to assess final outcomes between groups of patients with or without spikes at the time of medication tapering.

Transkutane Vagusnervstimulation

Background

Approximately 20-40?% of epilepsy patients show drug resistance and a large number of patients under antiepileptic therapy suffer from side effects including cognitive disorders and depression. Transcutaneous vagus nerve stimulation (t-VNS) can be used for these patients as a supplementary treatment to resection epilepsy surgery.

Aim

The main aims of this investigation were to test the safety, tolerability and practicality of t-VNS in epilepsy patients.

Material and methods

For the proof of concept trial ten patients with pharmacoresistant epilepsy (eight with focal and two with generalized epilepsy) were recruited. For admission to the study a minimum frequency of four seizures per month was necessary. The medication dosage was kept constant in the baseline and in the total treatment phase. The auricular branch of the vagus nerve (ABVN) of the left ear was stimulated. The stimulation pulses were biphasic with a frequency of 10/s and a pulse width of 300 µs. After an initial training period the stimulation was carried out in the morning, midday and evening for 1 h each over a period of 9 months. The subjectively experienced frequency of seizures, continuous video EEG (electroencephalogram) long-term conduction carried out 4 times for 1 week each and cognitive and functional alterations were considered to be end point parameters.

Results

The total treatment period of 9 months was completed by seven patients. Of these seven patients five showed a reduction in the frequency of seizures during the 9-month treatment period and two reported an increase in seizures. In two patients the seizure frequency was reduced by 45 % and 48 % in a comparison between baseline and end of treatment. In two further patients contradictions arose between the subjective report on seizure frequency and the objectively quantified frequency in the video EEG. For one patient the interictal epileptic EEG activity was continually reduced during the course of the 9-month period.

Conclusion

The t-VNS procedure represents a procedure which is well tolerated and practical for long-term treatment.     

Suppression of hippocampal epileptic seizures in the kainate rat by Poisson distributed stimulation

Purpose: Hippocampal deep brain stimulation (DBS) is an experimental therapy for patients with pharmacoresistant temporal lobe epilepsy (TLE). Despite the successful clinical application of DBS, the optimal stimulation parameters are undetermined. We evaluate the efficacy of a new form of DBS, using continuous stimuli with Poisson distributed intervals (Poisson distributed stimulation, PDS) in the kainate (KA) rat model, a validated model for human TLE. Methods: Status epilepticus was elicited by injection of KA (i.p.). After development of spontaneous seizures, rats were implanted with hippocampal DBS‐ and depth electroencephalography (EEG) electrodes. After baseline EEG monitoring, one group of rats (n = 13) was treated with PDS and a second (n = 11) received regular high frequency stimulation (HFS) at 130 Hz. Stimulation intensity was 100 μA below the threshold for induction of epileptiform EEG activity. Results: Stimulation intensity was significantly lower for PDS (156 ± 20 μA) than HFS (207 ± 23 μA; p < 0.02). Seven (54%) of 13 rats treated with PDS and 5 (45%) of 11 rats treated with HFS experienced a significant reduction in seizure frequency. In PDS‐improved rats, seizure frequency was reduced to 33% (p < 0.01) of baseline value and in HFS‐improved rats to 50% (p < 0.01). After termination of PDS, seizure rate returned to baseline value. Discussion: Continuous hippocampal PDS significantly reduces the number of spontaneous seizures. Compared to regular HFS, there is a slightly larger number of improved rats and a larger efficacy at a considerably lower stimulus intensity. The first two observations leave room for optimization, whereas a lower intensity is beneficial for battery life.     

Vagus nerve spiking activity associated with locomotion and cortical arousal states in a freely moving rat

The vagus nerve serves as a central pathway for communication between the central and peripheral organs. Despite traditional knowledge of vagus nerve functions, detailed neurophysiological dynamics of the vagus nerve in naïve behavior remain to be understood. In this study, we developed a new method to record spiking patterns from the cervical vagus nerve while simultaneously monitoring central and peripheral organ bioelectrical signals in a freely moving rat. When the rats transiently elevated locomotor activity, the frequency of vagus nerve spikes was correspondingly increased, and this activity was retained for several seconds after the increase in running speed terminated. Spike patterns of the vagus nerve were not robustly associated with which arms the animals entered on an elevated plus maze. During sniffing behavior, vagus nerve spikes were nearly absent. During stopping, the vagus nerve spike patterns differed considerably depending on external contexts and peripheral activity states associated with cortical arousal levels. Stimulation of the vagus nerve altered rat's running speed and cortical arousal states depending on running speed at the instant of stimulation. These observations are a new step for uncovering the physiological dynamics of the vagus nerve modulating the visceral organs such as cardiovascular, respiratory, and gastrointestinal systems.     

EEG changes with vagus nerve stimulation.

Vagus nerve stimulation (VNS) has been shown to induce EEG changes in animals, but human studies have not shown any significant acute EEG changes. This study is to determine the long-term effect of VNS on EEG. Twenty-one patients aged 4 to 31 years (mean: 14.1 +/- 7.0 years) were studied for a mean duration of 16.8 months with serial EEGs performed at baseline and at 3 months, 6 months, and 12 months after receiving a VNS implant. Five patients who showed active spikes/spike and wave activity on baseline EEGs were found to have synchronization of epileptiform activity, progressive increase in duration of spike-free intervals (P < 0.05), and progressive decrease in duration and frequency of spikes/spike and wave activity (P < 0.01) with time. The remaining 16 patients with less active baseline EEGs did not show obvious synchronization or clustering of spikes but also showed a statistically significant progressive decrease in the number of spikes on EEG with time (P < 0.004 at 3 months, P < 0.008 at 6 months, and P < 0.004 at 1 year). Vagus nerve stimulation induces progressive EEG changes in the form of clustering of epileptiform activity followed by progressively increased periods of spike-free intervals. This may reflect the mechanism of action of VNS in achieving seizure control: alternating synchronization and desynchronization of EEG, with the latter being progressively the dominant feature.     

Vagal and sciatic nerve stimulation have complex, time-dependent effects on chemically-induced seizures: a controlled study

Previous studies of the effects of electrical vagus stimulation on experimental seizures were without suitable controls or statistical validation, and ignored the potential role of vagally-induced hemodynamic depression on seizure expression. This study addresses these limitations. The effects of periodic left vagus nerve stimulation (LVNS) on chemically-induced seizures in rats were compared with control groups receiving no stimulation (NoS), left sciatic nerve stimulation (LSNS) and LVNS after pretreatment with methyl atropine (MA-LVNS). Stimulation followed a 30 s on-120 s off cycle over 130 min. Seizures were scored visually and the temporal variation of their probability P(s) across the stimulation cycle was measured statistically. P(s) was significantly different (P<0.01) for all groups: LSNS had the highest and MA-LVNS the lowest seizure probability; LVNS and NoS had intermediate values. While LVNS blocked seizures, it also precipitated them, explaining why its anti-seizure effect was only slightly greater than NoS. Neither LVNS nor MA-LVNS induced changes in cortical rhythms ('activation') associated with decreased P(s), unlike LSNS which increased cortical rhythm synchrony and with it, P(s). LVNS alone induced marked bradycardia and moderate hypoxemia. In conclusion, cranial and peripheral nerve stimulation have complex, time-varying effects on cerebral excitability: low frequency LSNS facilitated seizures, while LVNS both suppressed and facilitated them. The anti-seizure effect of LVNS was small and may have, in part, been due to a hemodynamically-induced deficit in energy substrates. The effects of MA-LVNS on seizure duration and P(s) raise the possibility that, in the absence of hemodynamic depression, stimulation of this nerve does not have a strong anti-seizure effect.     

High‐frequency oscillations in idiopathic partial epilepsy of childhood

Purpose: We explored high‐frequency oscillations (HFOs) in scalp sleep electroencephalography (EEG) studies of patients with idiopathic partial epilepsy (IPE) of childhood in order to obtain a better understanding of the pathologic mechanisms underlying IPE. Methods: The subjects were 45 patients, including 32 with benign childhood epilepsy with centrotemporal spikes (BCECTS) and 13 with Panayiotopoulos syndrome (PS). A total of 136 EEG records were investigated through temporal expansion and filtering of traces and time‐frequency spectral analysis. Key Findings: HFOs with frequency of 93.8–152.3 Hz (mean 126.2 ± 13.6 Hz) in the band of ripples were detected in association with spikes in 97 records (71.3%). Time from last seizure to the EEG recording was significantly shorter in those with spike‐related HFOs than in the EEG recordings with spikes without HFOs (p = 0.006). Although time from last seizure reflects age, age at the time of recording was not significantly different between EEG studies with and without HFOs. Peak‐power values of the high‐frequency spots in time‐frequency spectra were significantly negatively correlated with time from last seizure (R² = 0.122, p < 0.001) but not with age at the time of recording. Peak frequencies of the high‐frequency spectral spots were not significantly correlated with age at the time of recording or with time from last seizure. Significance: The close relationship between the generation of spike‐related HFOs and the period of active seizure occurrence indicated that HFOs may tell us more about epileptogenicity in IPE than the spikes themselves. Because there is a spectrum of pediatric epileptic disorders extending from the benign end of BCECTS to the encephalopathic end of epilepsy with continuous spike‐waves during slow‐wave sleep (CSWS), and HFOs that have already been detected in association with CSWS were more prominent than HFOs in IPE, intense spike‐related HFOs may indicate poor prognosis.     

Change of centrotemporal spikes from onset to remission in self-limited epilepsy with centrotemporal spikes (SLECTS)

ObjectiveTo reveal the changes of centrotemporal spikes that occur during the disease course of self-limited epilepsy with centrotemporal spikes (SLECTS).MethodWe retrospectively reviewed the serial EEGs of 63 patients with SLECTS from initial diagnosis to remission. There were 32 patients who did not undergo treatment and 31 patients who underwent treatment with oxcarbazepine (OXC). The change of occurrence or abundance, voltage, and location of centrotemporal spikes of serial EEGs were analyzed and compared between the two groups. Clinical seizure evidenced and reported was counted. The time gap between seizure remission and EEG remission was measured in the two groups.ResultChanges of occurrence or abundance of the centrotemporal spikes were either abrupt (sudden disappearance of the frequent spikes on following EEG) or gradual (decline in number over 2 or more serial EEGs). Pattern of spike disappearance was not significantly different between the medication naïve group and OXC treated group. The spike voltage or the location of centrotemporal spikes did not change during the disease course in most cases. Delay between seizure remission and EEG normalization was 3.34 ± 1.75 (mean ± standard deviation, range: 0.77–7.97) years in untreated patients and 3.03 ± 1.41 (0.95–6.61) years in OXC-treated group.ConclusionPattern of spike disappearance in SLECTS was either abrupt or gradual. Treatment with OXC had no effect in the disappearance pattern. Precise data regarding the pattern of disappearance and delay between seizure remission and EEG normalization can help to understand the evolution of spike in SLECTS and to predict the timing of normalization of EEG after seizure remission.     

Right-sided vagus nerve stimulation reduces generalized seizure severity in rats as effectively as left-sided

As currently utilized, vagus nerve stimulation (VNS) is applied to the cervical trunk of the left vagus nerve to suppress seizures clinically. Demonstration that VNS can also reduce seizure severity when electrodes are placed on the right cervical vagus nerve in rats would provide empirical evidence that the antiepileptic effects of VNS are not an exclusive property of the left vagus nerve. Rats were implanted with a custom cuff electrode on either the left or right cervical vagus nerve. Two days later, continuous VNS was begun in half the rats with left-sided and half with right-sided electrodes. The remaining rats were connected to the stimulator, but did not receive VNS. After 30s, pentylenetetrazole (PTZ) was administered systemically and seizures were rated by a blinded observer. The PTZ test was repeated two days later, with VNS administered to the previously unstimulated rats, while the others received no stimulation. VNS significantly reduced the severity of PTZ-induced seizures in rats regardless of the side of stimulation as compared to their no-VNS (control condition) seizure severity. No significant differences in efficacy existed based on the side of stimulation. These results indicate that right-sided VNS in rats is just as effective as left-sided VNS, suggesting that fibers necessary for seizure suppression are not unique to the left vagus nerve.     

Delta oscillation underlies the interictal spike changes after repeated transcranial direct current stimulation in a rat model of chronic seizures

BackgroundTranscranial direct current stimulation (tDCS) provides a noninvasive polarity-specific constant current to treat epilepsy, through a mechanism possibly involving excitability modulation and neural oscillation.ObjectiveTo determine whether EEG oscillations underlie the interictal spike changes after tDCS in rats with chronic spontaneous seizures.MethodsRats with kainic acid-induced spontaneous seizures were subjected to cathodal tDCS or sham stimulation for 5 consecutive days. Video-EEG recordings were collected immediately pre- and post-stimulation and for the subsequent 2 weeks following stimulation. The acute pre-post stimulation and subacute follow-up changes of interictal spikes and EEG oscillations in tDCS-treated rats were compared with sham. Ictal EEG with seizure behaviors, hippocampal brain-derived neurotrophic factor (BDNF) protein expression, and mossy fiber sprouting were compared between tDCS and sham rats.ResultsInterictal spike counts were reduced immediately following tDCS with augmented delta and diminished beta and gamma oscillations compared with sham. Cathodal tDCS also enhanced delta oscillations in normal rats. However, increased numbers of interictal spikes with a decrease of delta and theta oscillations were observed in tDCS-treated rats compared with sham during the following 2 weeks after stimulation. Resuming tDCS suppressed the increase of interictal spike activity. In tDCS rats, hippocampal BDNF protein expression was decreased while mossy fiber sprouting did not change compared with sham.ConclusionsThe inverse relationship between the changes of delta oscillation and interictal spikes during tDCS on and off stimulation periods indicates that an enhanced endogenous delta oscillation underlies the tDCS inhibitory effect on epileptic excitability.     

Neurophysiological effects of continuous cortical stimulation in epilepsy – Spike and spontaneous ECoG activity

ObjectiveThe effect of continuous subthreshold cortical stimulation (CSCS) over the seizure onset zone (SOZ) in epilepsy was analyzed to delineate the affected physiological processes.MethodECoG data was recorded over SOZ and adjacent regions in patients (n = 7) with refractory-epilepsy. Data was reviewed before and during 2 Hz cortical electrical stimulation. Group differences were estimated using ANOVA and correlation with Pearson’s r.ResultsCSCS reduced background ECoG power at SOZ (p < 0.05), increased spectral coherence (p < 0.05) and reduced spike rate (p < 0.01) over all recorded sites. Spectral power and coherence (p < 0.01) correlated with spike rate at SOZ but not with each other at any location. Spike morphology correlated with spike-rate over all recorded sites (p < 0.0001) and with spectral power and coherence at SOZ (p < 0.01).ConclusionThis study shows changes in cortical electrophysiology during CSCS over the SOZ where spike rate reduction correlated with two independent electrophysiological parameters, background power and coherence. These results suggest the possibility of a causal relationship between spectral power, coherence and interictal spikes which may be related to seizure rate.SignificanceImproved understanding of the effect of electrical stimulation on epileptic tissue could suggest improvements in stimulation paradigms to reduce seizure frequency.     

Modulation of seizure threshold by vagus nerve stimulation in an animal model for motor seizures

De Herdt V, De Waele J, Raedt R, Wyckhuys T, El Tahry R, Vonck K, Wadman W, Boon P. Modulation of seizure threshold by vagus nerve stimulation in an animal model for motor seizures.
Acta Neurol Scand: 2010: 121: 271–276.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – The precise mechanism of action of vagus nerve stimulation (VNS) in suppressing epileptic seizures remains to be elucidated. This study investigates whether VNS modulates cortical excitability by determining the threshold for provoking focal motor seizures by cortical electrical stimulation before and after VNS. Material and methods – Male Wistar rats (n = 8) were implanted with a cuff‐electrode around the left vagus nerve and with stimulation electrodes placed bilaterally on the rat motor cortex. Motor seizure threshold (MST) was assessed for each rat before and immediately after 1 h of VNS with standard stimulation parameters, during two to three sessions on different days. Results – An overall significant increase of the MST was observed following 1 h of VNS compared to the baseline value (1420 μA and 1072 μA, respectively; P < 0.01). The effect was reproducible over time with an increase in MST in each experimental session. Conclusions – VNS significantly increases the MST in a cortical stimulation model for motor seizures. These data indicate that VNS is capable of modulating cortical excitability.     

迷走神经刺激术-程控电刺激治疗难治性癫痫

目的 应用迷走神经刺激术(vagus nerve stimulation，VNS)治疗难治性癫痫，并探讨其治疗机制和方法。方法 个体化的VNS疗效预测和精确无误的VNS植入，适时恰当的刺激参数程控调校，并以长程脑电图、SPECT观测VNS带来的脑功能改变。结果 接受VNS术3个月后，3例病患的发作频次均减少50％以上，2例在应急磁铁的辅助下基本不再表现复杂性发作，1例不再表现全身失张性发作，而以部分性发作为主，偶有复杂发作，生活质量提高。脑电图原有的棘波、尖波消失或减少，阵发性异常消失或时间缩短。发作间期SPECT表现为原有的低代谢灶缩小。结论 恰当地应用VNS能够为难治性癫痫提供一种有效、微创、副作用极少的治疗手段。     

EEG spike activity precedes epilepsy after kainate‐induced status epilepticus

Purpose: Chronic epilepsy frequently develops after brain injury, but prediction of which individual patient will develop spontaneous recurrent seizures (i.e., epilepsy) is not currently possible. Here, we use continuous radiotelemetric electroencephalography (EEG) and video monitoring along with automated computer detection of EEG spikes and seizures to test the hypothesis that EEG spikes precede and are correlated with subsequent spontaneous recurrent seizures. Methods: The presence and pattern of EEG spikes was studied during long recording epochs between the end of status epilepticus (SE) induced by three different doses of kainate and the onset of chronic epilepsy. Results: The presence of spikes, and later spike clusters, over several days after SE before the first spontaneous seizure, was consistently associated with the development of chronic epilepsy. The rate of development of epilepsy (i.e., increase in seizure frequency) was strongly correlated with the frequency of EEG spikes and the cumulative number of EEG spikes after SE. Conclusions: The temporal features of EEG spikes (i.e., their presence, frequency, and pattern [clusters]) when analyzed over prolonged periods, may be a predictive biomarker for the development of chronic epilepsy after brain injury. Future clinical trials using prolonged EEG recordings may reveal the diagnostic utility of EEG spikes as predictors of subsequent epilepsy in brain‐injured humans.     

Vagus Nerve Stimulation Induces a Sustained Anticonvulsant Effect

Summary: Purpose: Stimulation of the vagus nerve can effectively abort several types of experimentally induced seizures in animals when administered near the time of seizure onset. Indirect evidence from human trials and animal studies suggests that the anticonvulsant effects of vagus nerve stimulation (VNS) extend beyond the duration of stimulation. We used the pentylenetetrazol model to determine whether VNS exerts a persistent anticonvulsant effect.
Methods: VNS (1 mA, 30 Hz, 500 μs pulse width) was administered continuously for 0, 1, or 60 min, or intermittently (30 s on, 5 min off) for 60 min, to awake and freely moving animals. After the end of stimulation, pentylenetetrazol (50 mg/kg i.p.) was administered to induce seizures. Time-course studies were also performed, consisting of 60 min of VNS followed by pentylenetetrazol injection after 0, 3-, 5-, and 10-min intervals.
Results: The greatest anticonvulsant effect occurred after 60 min of continuous VNS, which prevented convulsions in four of 12 rats and reduced significantly seizure duration, the total number of seizures, and number of tonic seizures. Intermittent VNS was less effective than continuous stimulation for 60 min, but more effective than that for 1 min. The anticonvulsant effect declined in a time-dependent fashion after discontinuation of VNS, with return to nonstimulated control values by 10 min.
Conclusions: The results of this study verify a persistent VNS-induced anticonvulsant effect and indicate that its efficacy is dependent on the cumulative stimulus duration.     

Terapia con estimulación del nervio vago en pacientes con epilepsia fármaco-resistente y callosotomía previa

ObjectiveTo analyse the results of vagus nerve stimulation in patients with drug-resistant epilepsy and previous corpus callosotomy.Materials and methodsWe prospectively reviewed data from patients with drug-resistant epilepsy who showed persistence of disabling seizures after undergoing corpus callosotomy, in whom it was not possible to identify an epileptogenic focus and who were subsequently treated with vagus nerve stimulation.Variables analysed included: age, gender, aetiology of epilepsy, frequency and characteristics of the crises and Engel scale classification, before and after vagal stimulator implant. Furthermore, the percentage differences in seizure frequency changes were also calculated.ResultsFour patients were identified: two male and two female. The total seizure frequency had decreased between 20% and 81% after corpus callosotomy in three patients and one of them did not show any favourable response (Engel IVB). Following implantation of the stimulator they became reduced to between 57% and 100% after a mean follow-up period of 8.3 months (range: 3 to 12 months). Generalised seizures decreased between 71.4% and 100%, and focal seizures between 57.7% and 100%.ConclusionsVagus nerve stimulation therapy proved to be an alternative for the reduction of seizure frequency in patients with drug-resistant epilepsy who suffered disabling seizures despite undergoing corpus callosotomy as primary surgery.     

The relationship between sleep and epilepsy

The occurrence of seizures in the sleep state is observed in nearly one third of patients. This is caused by an intimate relationship between the physiological state of sleep and the pathological process underlying epileptic seizures. Both sleep and sleep deprivation influence the frequency of epileptiform discharges on electroencephalograms as well as the occurrence of clinical seizures, typically during nonrapid eye movement sleep. The relationship of epileptiform activity to nonrapid eye movement sleep is vividly shown in the syndrome of continuous spikes in slow-wave sleep and the Landau-Kleffner syndrome. Seizure semiology can also be influenced by sleep and sleep deprivation. Sleep disorders may influence seizure control, and effective treatment of sleep disorders can improve seizure control. Seizures, antiepileptic drugs, ketogenic diet, and vagus nerve stimulation all influence sleep quality, daytime alertness, and neurocognitive function.     

红藻氨酸诱导大鼠癫痫发作的电生理机制研究

目的　探讨红藻氨酸 ( KA)诱导大鼠复杂部分性癫痫发作的 EEG特点以及可能的电生理起搏点位置。方法　在立体定位指引下 ,将 EEG记录电极植入 1 2只大鼠双侧海马、额叶皮质或杏仁核中 ,其中 8只为实验组 ,4只为对照组。手术后 1周在大鼠清醒状态下 ,连续描记 KA或盐水注射后 EEG 1 2 0 min,观察 EEG波形、波幅以及频率的变化特点并记录每次电发作的起搏点位置。结果　 ( 1 ) KA注射后大鼠 EEG表现出多种形式的放电波形 ,典型波形有单棘波、多棘波、多相棘波、正相棘波、棘节律、节律性慢波、棘慢波等。 ( 2 )大鼠在凝视发作以及自动症发作时海马、杏仁核和额叶皮质均有异常放电。 ( 3) KA注射后大鼠电发作起搏点不固定。 ( 4 )各导放电频率多数情况下一致 ,偶有不一致现象。 ( 5 )存在亚临床放电。结论　 ( 1 ) KA注射后大鼠 EEG表现为多种形式的电发作活动 ;( 2 )大鼠在复杂部分性发作过程中不仅有边缘系统参与 ,也有边缘外额叶皮质参与 ;( 3)KA模型中 ,电发作起搏点不固定 ,KA注射后大鼠脑内可能存在一个异常的神经元网络 ,在网络中存在放电不均衡现象。     

Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 years

We assessed the long-term efficacy of vagus nerve stimulation (VNS) in 64 refractory epilepsy patients. After implantation, intermittent stimulation was delivered and seizure frequency and severity were counted. Average treatment time was 20 months. Nineteen of 47 patients with partial seizures, five of nine patients with idiopathic generalized seizures, and five of eight patients with Lennox-Gastaut syndrome had >50% seizure reduction. Side effects were mild. VNS is a safe and effective treatment for refractory epilepsy.     

EEG Patterns of Grand Mal Seizures Occurring Under Different Recording Conditions

Thirty-five EEG patterns of grand mal seizures recorded under some conditions such as awake-rest, sleep activation, beme-gride activation and intermittent photic stimulation were studied in 31 epileptics and four non-epileptics. Preictal EEG's were generally variable in comparison with ictal EEG's. It was not till 10 sec before seizures that the incidence of seizure discharges changed in most all cases, of which six increased and four decreased. A paroxysmal extreme varied EEG abnormality often continued for several to several ten sec immediately before a tonic phase, associated with some clinical symptoms. EEG patterns of the “preconvulsive phase” were divided into six types with different clinical features. In most all cases of bamegride activation, poly-spike and wave discharges preceded on seizure activities and some of them related with absence or psychomotor epilepsies. In all cases of sleep activation and photic stimulation, high voltage slow bursts or poly spikes preceded. Seizure patterns recorded at awake-rest were indefinite. A few cases didn't show any preconvulsive EEG changes, and were closely related with grand mal epilepsies. While the grand mal seizure during sleep had a long tonic-clonic convulsive phase and a short pre- and postconvulsive phase, that induced by bemegride activation showed the opposite findings. The grand mal seizure at awake-rest had the middle tendency between the two. The differences among the effects of various recording conditions on seizure patterns present some suggestions as to the patho-physiological mechanism of epileptic seizures.