Audiogenic kindling in the Wistar rat: a potential model for recruitment of limbic structures

Repetitive high intensity (110 dB) sound stimulation induces a forebrain-kindling phenomenon in animals predisposed to sound induced seizures. Wistar audiogenic rats (WARs) have been reported to develop a mixed brainstem-limbic seizure pattern, after more than five to ten stimuli. Besides the original brainstem wild running and tonic-clonic seizures, new behavioral patterns appear resembling those of electrical amygdala kindling. Although audiogenic kindling is a well-known phenomenon, electrographic limbic recruitment during the kindling has never been reported. Our objective was to use electrophysiology to test the hypothesis of gradual and sequential involvement of the amygdala and then cortex during audiogenic kindling. We used video-EEG recordings with cortical and deep electrode implants (inferior colliculus and basolateral amygdaloid nuclei) during audiogenic kindling on eight WARs, and their respective controls, submitted to a protocol of three acoustic stimuli per day. A new design for 'on site' source follower circuits was used in order to minimize noise during the recording of EEG data from the wild running episode and the subsequent tonic-clonic or motor limbic seizures. The video-EEG equipment assembled allowed synchronous recordings of both behavior and EEG. WARs first recordings showed electrodecremental responses after seizure onset and a probable epileptiform activity, particularly in the inferior colliculus, during the tonic phase of seizure. All animals showed very similar polyspike-wave activity in the amygdala, after behavioral seizure patterns (Racine's scale) occurred. The morphology of such epileptiform EEG activity is very similar to that reported for electrical amygdala kindling. Also, when audiogenic kindling continued, both inferior colliculus and cortical electrodes presented high amplitude and synchronized epileptiform polyspike activity.     

Effect of lactation on the expression of audiogenic seizures: association with plasma prolactin profiles

Female Wistar rats and Wistar audiogenic rats (WARs) were used to investigate the potential roles of prolactin (PRL) and progesterone in the modulation of seizure expression. Animals were screened for seizure severity in both groups. All WARs at least displayed tonic-clonic convulsions followed by clonic spasms (TC) whereas none of the Wistar rats displayed seizures (Resistant). After seizures the plasma level of PRL in nulliparous female WARs increased about 8-fold compared to their basal levels and to the levels of Resistant animals. This value was still significantly higher than basal levels 15 min later. Lactation produced a decrease in the TC proportion in seizures in WARs both with and without pups. Two sub-populations of animals could be characterized: one that had TC suppressed (low seizure severity; LSS) and one that did not (high seizure severity; HSS). In animals of the LSS subgroup, either with or without pups, seizure severity decreased gradually and lowest values were seen on the 30th day after delivery. The temporal profile of plasma PRL during a 90-min period of suckling without sound stimulation showed significantly higher levels for LSS, the HSS levels being similar to those of the Resistant group. A progressive decrease in the group means for progesterone plasma concentration between the 9th and 29th days of lactation was detected in Resistant rats (P<0.05) but not in WARs. No significant differences between groups were revealed by comparison of the overall means. Taken together these data confirm the presence of a clear-cut post-ictal PRL peak after TC with a decrease in seizure severity in female WARs with and without pups. An eventual long-term role of PRL in modulating seizure activity might be related to the multifactorial physiological conditions of both pregnancy and lactation.     

EEG wavelet analyses of the striatum-substantia nigra pars reticulata-superior colliculus circuitry: audiogenic seizures and anticonvulsant drug administration in Wistar audiogenic rats (War strain)

The importance of the substantia nigra pars reticulata (SNPr), striatum (STR) and superior colicullus (SC) in the blockade of experimental seizures is well known. But, in audiogenic seizures (brainstem tonic-clonic seizures), the anticonvulsant activity of these nuclei is still controversial. In the present study we aimed to analyze the STR-SNPr-CS circuitry in the audiogenic seizures of Wistar audiogenic rat (WAR). Behavioral and electroencephalographic (EEG) data were collected from WARs under no treatment or injection with systemic (phenobarbital) or intracerebral (intranigral) drugs (muscimol and phenobarbital). The main EEG frequency oscillation of STR, SNPr and SC seen before, during and after audiogenic seizures or during seizure protection, was determinated with wavelet spectral analyses. This method allows the association between behavior and EEG (video-EEG). Audiogenic seizures last only for half a minute in average, suggesting that the interruptions of seizures are probably not due to exhaustion. Systemic phenobarbital caused an acute and dose-dependent behavioral and EEGraphic anticonvulsant effect both in WARs. The dose of phenobarbital 15mg/kg protected animals almost completely, without side effects such as ataxia and sedation. In our data, this endogenous "natural" seizure blockade (or termination) seems to be similar to the "forced" seizure abolition, like the one caused by a systemic non-ataxic phenobarbital dose, because in both cases an intense decrease in the EEG main frequency oscillation can be seen in SNPr and SC. Intranigral phenobarbital or muscimol did not protect animals, and actually induced an increase in the main EEG frequency oscillation in SC. The main finding of the present study is that, in contrast to what is well believed about the incapacity to control audiogenic seizures by the striato-nigro-tectal circuitry, we collected here evidences that these nuclei are involved in the ability to block these seizures. However, the striato-nigro-tectal circuitry in WARs, a genetically developed strain, seems to have different functional mechanisms when compared with normal rats.     

Anatomical and behavioral analyses of the inheritance of audiogenic seizures in the progeny of genetically epilepsy-prone and Sprague-Dawley rats

Our previous studies have shown an increase in the number of GABAergic and total neurons in the inferior colliculus (IC) of the genetically epilepsy-prone rat (GEPR-9) as compared to the non-seizing Sprague-Dawley (SD) rat. To determine whether an increase in neuron number in the IC is genetically associated with seizure behavior, seizing and non-seizing offspring of GEPR-9 and SD progenitor strains were studied as well as offspring from backcrosses made with F1 and either GEPR-9 or SD rats. In addition, the ontogeny of seizure behavior was studied in seizing rats from these same backgrounds. The development of seizure behavior in GEPR-9s was shown to be dependent on age and the number of exposures to sound stimulus up until the age of 9 weeks. The F1 and F2 generations displayed different audiogenic seizure profiles than those of the two progenitor strains. In the F1 generation, the ratio of seizing to non-seizing rats was always greater than 3:1, and the distribution of seizure scores was similar for males and females. In addition, the off-spring from backcrosses made with F1 rats (high or low seizing) and GEPR-9s displayed maximal audiogenic response scores (ARS) of 9, a characteristic of the GEPR-9s used in this study. The results of these genetic studies indicate a polygenetic inheritance of this autosomal dominant trait of audiogenic seizure susceptibility. For the quantitative study of neuronal density in the IC, neurons were counted from cresyl violet-stained preparations from seizing and non-seizing F1 and F2 rats, backcrosses from different categories and age-matched SD rats. Statistically significant increases in the number of both small (70% increase) and medium-sized (14% increase) neurons occurred in the high seizing animals (ARS = 7-9) as compared to either the non-seizing F2 or SD rats. In addition, a significant increase in the number of small neurons (77% increase) occurred in the high seizing offspring of the F1 X GEPR-9 backcross as compared to that of the non-seizing offspring of the F1 X SD backcross. The data from 25 rats generated a 0.9 coefficient of linear correlation between ARS and the number of small neurons. The results from the anatomical studies suggest that the inheritance of audiogenic seizures appears to be closely linked to the increase in cell number. Therefore, the increase in cell number in the IC may be an important determinant of seizure behavior for GEPR-9s.     

Effect of precollicular transection on audiogenic seizures in genetically epilepsy-prone rats

Previous studies have demonstrated that generalized tonic-clonic seizures (GTCS) consisting of running/bouncing clonic and tonic extension can still be elicited in rats after brain transections which separate forebrain from brain stem, showing that forebrain circuitry is not required for GTCS. Inasmuch as sound-induced generalized tonic-clonic seizures in rodents are characterized by running-bouncing clonic and tonic convulsions, we have hypothesized that these are brain stem seizures that can occur independently of the forebrain. To test this hypothesis, we examined the response of two strains of genetically epilepsy-prone rats (GEPR-3s and GEPR-9s) to seizure-evoking auditory stimuli 3 h after a precollicular transection or sham surgery performed under ether anesthesia. In addition, the effect of a precollicular transection on audiogenic seizures was evaluated in normal rats made susceptible to such seizures by infusing NMDA into the inferior colliculus. Following the transection 58% of GEPR-9s displayed a sound-induced tonic-clonic convulsion and the remaining 42% exhibited a sound-induced seizure when subjected to stimulation 5 min after a subconvulsant dose of pentylenetetrazol (PTZ). While sham surgery and the precollicular transection both reduced sound-induced seizure severity in GEPR-3s, the full seizure response could be elicited by sound stimulation following a subconvulsant dose of PTZ. Moreover, the audiogenic seizures in normal rats rendered susceptible by NMDA were unaltered by the precollicular transection. These findings show that the anatomical circuitry required for generalized tonic-clonic seizures evoked by sound stimulation in rodents resides within the brain stem.     

Increased secondary generalization of partial seizures after temporal lobectomy

OBJECTIVE: This study tests the primary hypothesis that secondary generalization of partial seizures is more likely after anterior temporal lobectomy (ATL) than before ATL, and the secondary hypothesis that antiepileptic drug withdrawal accounts for increased generalization of seizures postoperatively. BACKGROUND: The authors observed that some patients had generalized tonic-clonic (GTC) seizures after but not before ATL, by using a new classification of outcome that compares preoperative and postoperative seizure frequencies by seizure type. METHODS: Twenty patients with refractory temporal lobe epilepsy had postoperative GTC seizures or nongeneralizing complex partial (CP) seizures in a consecutive ATL series. All had reduced seizure frequency postoperatively and more than 2 years of follow-up on antiepileptic drugs. The authors calculated a generalization fraction, as (number of GTC seizures)/(number of CP and GTC seizures), for 2 years before and 2 years after surgery. RESULTS: Postoperative generalization fractions were greater than preoperative generalization fractions (Wilcoxon signed-rank test, p < 0.01). Most postoperative GTC seizures were not associated with antiepileptic drug withdrawal, and postoperative GTC seizures were not more associated with drug withdrawal than were postoperative CP seizures. Patients with more than two GTC seizures per year preoperatively were more likely than other patients to have postoperative GTC seizures. CONCLUSIONS: Patients with reduced seizure frequency after ATL have a greater tendency for partial seizures to secondarily generalize postoperatively. This phenomenon is not explained by antiepileptic drug withdrawal.     

Characterization of audiogenic-like seizures in naive rats evoked by activation of AMPA and NMDA receptors in the inferior colliculus

The role of glutamate receptors in the inferior colliculus (IC) in audiogenic and audiogenic-like seizures was investigated in adult rats with transient neonatal hypothyroidism by 0.02% propylthiouracil (PTU) treatment through mother's milk (PTU rats) and in naive rats treated intracisternally with N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), or cyclothiazide, an inhibitor of rapid AMPA receptor desensitization. All rats showed audiogenic or audiogenic-like seizures characterized by running fit (RF) and generalized tonic-clonic seizures (GTCS). While systemically administered MK-801 inhibited GTCS, intracisternally administered NBQX inhibited RF and GTCS in both audiogenic and audiogenic-like seizures. Auditory stimulation shortened the latency to GTCS induced by AMPA, but not NMDA, at a subclinical dose and further elongated the shortened duration of RF, but not GTCS, induced by MK-801 pretreatment. Furthermore, Northern blot analysis was used to evaluate the expression of the immediate-early gene c-fos in the IC following induction of audiogenic or audiogenic-like seizures. The significant induction of c-fos mRNA by audiogenic seizures in PTU rats or by AMPA- or cyclothiazide-induced seizures in naive rats was prominent in the IC. MK-801 suppressed c-fos mRNA expression in the IC induced by audiogenic seizures in PTU rats or by AMPA-induced seizures in naive rats. NBQX suppressed the expression of c-fos mRNA in the IC induced by AMPA-induced seizures but did not suppress c-fos mRNA in PTU rats or rats with cyclothiazide-induced seizures. Auditory stimuli failed to affect c-fos mRNA induction by AMPA. The present study suggests that audiogenic-like seizures can be reproduced by glutamate receptor agonists in which AMPA receptors are primarily linked to the initiation of audiogenic seizures (RF) while NMDA receptors presumably located within the IC are involved in the propagation of GTCS in audiogenic seizures.     

Lateralizing value of asymmetric tonic limb posturing observed in secondarily generalized tonic-clonic seizures

PURPOSE: A striking asymmetry of limb posture occurs during secondarily generalized tonic-clonic (GTC) seizures wherein one elbow is extended while the other is flexed during the tonic phase of the GTC seizure. We have named this phenomenon asymmetric tonic limb posturing (ATLP) or the "Figure 4 Sign." METHODS: Fifty-nine secondarily GTC seizures from 31 patients with partial epilepsy who underwent successful epilepsy surgery were analyzed, in addition to another group of 64 GTC and generalized clonic seizures from 26 patients collected prospectively over a 7-month period. Three observers reviewed these seizures blinded to the side of ictal EEG onset and other clinical data. RESULTS: The extended elbow was contralateral to the side of ictal onset in 35 of 39 patients who had ATLP during their seizures. The kappa index, a measure of interobserver agreement, was calculated, and ATLP was found to have very good agreement between observers. CONCLUSIONS: In secondarily generalized tonic-clonic seizures, ATLP (Figure 4 Sign) may sometimes be only available lateralizing sign.     

Spectrum of epilepsy in neurocysticercosis: a long-term follow-up of 143 patients

To characterize the clinical profile and the prognostic factors of the epilepsy due to parenchymal neurocysticercosis (NCC) 143 patients were analysed. Patients (62 men, 81 women) had a mean age at epilepsy onset of 29 years (range 2-71), mean epilepsy duration of 16 years (range 1-58) and mean follow-up of 5.2 years. Seizures were generalised tonic-clonic (GTC) in 50 patients (35%), simple partial (SP) in 66 (46%) and complex partial (CP) in 27 (19%). Epilepsy began as a single seizure in 73% and as a cluster of seizures or status epilepticus in 27%. Seizures were controlled in 64% of patients. Multivariate analysis revealed that significant prognostic factors associated with seizure control were type of seizures and age at epilepsy onset. Control is more likely in GTC and SP seizures and in patients with a higher age at seizures onset. Our analysis establishes that epilepsy due to NCC is a heterogeneous syndrome concerning age and mode of onset, seizure type, duration of epilepsy and pattern of evolution probably related with different pathogenic mechanisms.     

Audiogenic seizures in Wistar rats before and after repeated auditory stimuli: clinical,pharmacological, and electroencephalographic studies

Summary A strain of Wistar rats was inbred for susceptibility to audiogenic seizures characterized by one or two wild running fits followed by tonic dorsiflexion with open mouth and then a catatonic state. During the tonic phase, the cortical EEG was flat for 1 to 2 sec, then changed to a slow, regular lowamplitude discharge, 9 to 12c/s, for 25 to 60 sec. In these rats exposed to 40 daily 90-sec auditory stimuli, behavior and EEG changed. The wild running became disorganized by myoclonic jerks of the limbs and body. In some animals, the tonic extension disappeared and a myoclonic seizure developed progressively, with facial and forelimb clonus, and rearing and falling. In others, the tonic phase was followed by a generalized clonic phase. The EEG during the myoclonic and tonic-clonic seizures showed high-amplitude rhythmic spikes, polyspikes and spike-waves, 1 to 10 c/s, for 40 to 120 sec, often outlasting the sound stimulus. The effects of ethosuximide, carbamazepine and phenytoin were the same on primary and modified audiogenic seizures. The progressive behavioral and EEG modifications of audiogenic seizures following repeated auditory stimuli suggest that kindling had developed, the seizures being propagated from the brain stem to forebrain structures.     

Audiogenic seizures and the pineal gland

The effects of sound stimulation (electric bell, 110 dB) on the pineal glands of adult female rats were studied. Two types of animals were selected: audiogenic (Adg) and nonaudiogenic (Nadg). Unlike the Nadg rats, Adg rats exhibited tonic-clonic seizures in response to stimulation. In Adg rats, after a single seizure, all pinealocyte nuclei were pyknotic and the characteristic lobular organization of the pineal was markedly disrupted, indicating intense glandular stress; however, neither serotonin levels nor its biosynthesis were significantly altered. These results suggest a physiopathological relationship between audiogenic seizures and the pineal gland.     

The effect of nimodipine on picrotoxin-induced seizures

The effects of the calcium channel antagonist, nimodipine, on picrotoxin-induced myoclonic (MYO) and generalized tonic-clonic (GTC) seizures were investigated in male and female rats. In males, a dose-response study of nimodipine's effects on seizures induced by different doses of picrotoxin was conducted. In a second experiment, female rats were tested for latency to and incidence of MYO and GTC seizures after being pretreated with nimodipine 2 hr, 24 hr, or 72 hr prior to seizure testing. The results showed that, in males, various doses of nimodipine significantly increased the mean latencies to MYO and GTC seizures and significantly reduced the incidence of GTC seizures. In females, nimodipine significantly reduced the incidence and/or increased the latency of GTC seizures when given 24 hr of 72 hr prior to administration. In addition to the anticonvulsant effects, nimodopine significantly increased survival after seizures in both males and females even when it had no significant effects on seizure incidence or latency. The results of this study support the hypothesis of calcium involvement in seizure induction. However, the sex- and time-dependent nature of the nimodipine effects as well as the effects of nimodipine on survival after seizures suggest that the relationship between calcium and seizure activity is complex.     

Exacerbation of Partial Seizures and Onset of Nonepileptic Myoclonus with Carbamazepine

A child had two to three generalized tonic-clonic (GTC) seizures per week unresponsive to phenobarbital (PB) and valproate (VPA). Interictal EEG demonstrated left occipital spikes. When carbamazepine (CBZ) therapy was started, he developed very frequent (4-6/day) complex partial seizures (CPS) characterized on ictal EEG by focal right temporal lobe discharges. The seizure exacerbation, which was associated with development of nonepileptic, multifocal myoclonus, resolved 24 h after CBZ was discontinued. The exacerbation occurred with therapeutic CBZ serum levels, but may have been related to the toxic levels of carbamazepine-10, 11-epoxide (CBZE).     

Long-Term Course of Childhood Epilepsy with Intractable Grand Mal Seizures

Abstract: Twenty-nine children with childhood epilepsy characterized by frequent grand mal (generalized tonic-clonic) seizures in spite of maximal doses of antiepileptic drugs and by an early onset of seizures (before 1 :year of age) were followed up for more than 5 :years. The children were divided into 3 :groups: severe myoclonic epilepsy in infancy (SME), no SME, and intractable childhood epilepsy with generalized tonic-clonic seizures (GTC). In all the 3 :groups, the grand mal seizures persisted, whereas the other types of seizures tended to disappear as the patients aged, and the prognosis for mental development was poor. In the majority of cases in all the 3 :groups, the waking grand mal seizures altered to sleep grand mal seizures with aging. Two pairs of monozygotic twins with SME suggested that genetic factors play a role in this epileptic syndrome. Intractable childhood epilepsy with GTC is distinguished by the absence of other types of generalized seizures. It cannot be regarded as an epileptic syndrome, but its pathogenesis and treatment require further studies.     

Behavioral and EEG effects of GABAergic manipulation of the nigro-tectal pathway in the Wistar audiogenic rat (WAR) strain II: an EEG wavelet analysis and retrograde neuronal tracer approach

The role of the substantia nigra pars reticulata (SNPr) and superior colliculus (SC) network in rat strains susceptible to audiogenic seizures still remain underexplored in epileptology. In a previous study from our laboratory, the GABAergic drugs bicuculline (BIC) and muscimol (MUS) were microinjected into the deep layers of either the anterior SC (aSC) or the posterior SC (pSC) in animals of the Wistar audiogenic rat (WAR) strain submitted to acoustic stimulation, in which simultaneous electroencephalographic (EEG) recording of the aSC, pSC, SNPr and striatum was performed. Only MUS microinjected into the pSC blocked audiogenic seizures. In the present study, we expanded upon these previous results using the retrograde tracer Fluorogold (FG) microinjected into the aSC and pSC in conjunction with quantitative EEG analysis (wavelet transform), in the search for mechanisms associated with the susceptibility of this inbred strain to acoustic stimulation. Our hypothesis was that the WAR strain would have different connectivity between specific subareas of the superior colliculus and the SNPr when compared with resistant Wistar animals and that these connections would lead to altered behavior of this network during audiogenic seizures. Wavelet analysis showed that the only treatment with an anticonvulsant effect was MUS microinjected into the pSC region, and this treatment induced a sustained oscillation in the theta band only in the SNPr and in the pSC. These data suggest that in WAR animals, there are at least two subcortical loops and that the one involved in audiogenic seizure susceptibility appears to be the pSC-SNPr circuit. We also found that WARs presented an increase in the number of FG+ projections from the posterior SNPr to both the aSC and pSC (primarily to the pSC), with both acting as proconvulsant nuclei when compared with Wistar rats. We concluded that these two different subcortical loops within the basal ganglia are probably a consequence of the WAR genetic background.     

Absence seizures with evolution into generalized tonic-clonic activity: clinical and EEG features

PURPOSE: To report the clinical and electrographic features of absence seizures evolving into generalized tonic-clonic (GTC) activity in six patients with idiopathic generalized epilepsy. METHODS: All patients were referred for evaluation of refractory seizures and underwent video-EEG monitoring after discontinuation of their antiepileptic drugs (AEDs). We analyzed the video-EEG recordings for seizure semiology as well as ictal and interictal activity. We also reviewed the initial clinical data in all patients. RESULTS: All patients were women, with a mean age of 27 years (range, 14-43 years). The mean age at seizure onset was 12 years (range, 5-15 years). Family history was positive for epilepsy in four patients. All patients had recorded seizures with an onset that was characteristic of generalized absence clinically and electrographically, with evolution into GTC activity. The EEG onset was with generalized 2.5-to 5-Hz spike-and-wave discharges, with evolution into faster rhythmic activity. Interictal EEG recordings showed generalized 2-to 5-Hz spike-and-wave discharges. All had normal background activity. All patients were treated with divalproex monotherapy. Five patients have been seizure free, and one had a single breakthrough GTC seizure during a follow-up period of 12-36 months. CONCLUSIONS: GTC activity may evolve from typical absence seizures. This seizure type should be included in the International Classification of Seizures. Its recognition and distinction from complex partial seizures with secondary generalization are important for appropriate therapy.     

Gender difference in susceptibility to picrotoxin-induced seizures is seizure- and stimulation-dependent

In a dose-response study, the pattern of sex-associated susceptibility to picrotoxin-induced myoclonic, focal, akinetic, and generalized tonic-clonic (GTC) seizures was investigated in rats to determine whether the reported heightened susceptibility of females to seizures was a general phenomenon in rats or whether it was limited to specific types of seizures. The latency to and incidence of specifically categorized seizures were used as indices of susceptibility after male and female rats had been injected with picrotoxin (3-10 mg/kg). The results revealed that at low doses of picrotoxin (4 mg/kg), female rats had significantly shorter latencies to myoclonic seizures and significantly shorter latencies and higher incidences of GTC seizures. At higher doses of picrotoxin (8 and 10 mg/kg), the pattern of relative susceptibility of males and females to myoclonic seizures was reversed, with males having shorter latencies than females. There were no significant sex differences in the incidence of or latency to focal or akinetic seizures at any of the doses tested. These findings indicate 1) that there are significant sex differences in seizure susceptibility only for specific seizure categories in rats; and 2) that for seizure categories where significant sex differences were identified, the observed pattern of relative susceptibility of males and females depends on the dose of picrotoxin tested. Thus, patterns of sex-associated seizure susceptibility favoring either males or females are both seizure- and stimulation-limited and do not reflect general dispositions to seizures in either sex.(ABSTRACT TRUNCATED AT 250 WORDS)     

Corpus callosotomy in refractory idiopathic generalized epilepsy

RATIONALE: A small percentage of patients with idiopathic generalized epilepsy (IGE) do not respond to medical therapy. Generalized tonic-clonic (GTC) seizures are especially debilitating and can be associated with severe injuries. The benefit, safety and effect of corpus callosotomy (CC) in patients with IGE have not been studied. METHODS: We reviewed patients with presumed IGE who underwent CC between 1991 and 2000. Criteria for selection included history, examination, brain imagining, interictal and ictal EEG. All patients had refractory and debilitating tonic-clonic seizures (GTCS) and had failed four or more antiepileptic drugs. Seizure frequency was calculated per month over the last year and pre-operative baseline was compared to last follow-up using paired t-tests. IQ, executive function, language and verbal, non-verbal memory and quality of life (QOL) was compared before and after surgery. Serial EEGs after surgery were reviewed. RESULTS: There were nine patients (seven men), mean age 37.9 (range: 22-49), mean IQ 87.3 (range: 75-107). All had anterior CC. Mean follow-up time was 5.4 years (range: 0.6-10.3 years). One patient died from sudden death in epilepsy 9 months after surgery. There was a significant reduction of GTC seizures from 6.3 to 1.1 (p<0.005). Four patients had more than 80% and eight more than 50% reduction. Of five patients with absence seizures, two became seizure free and one had more than 80% reduction and two worsened slightly, and of three with myoclonic seizures one had more than 90% reduction. One patient had completion of the CC with improvement of myoclonus and absence seizures, but not of GTC seizures and suffered a disconnection syndrome. Another had right frontal focal resection without improvement after new seizures of focal onset. Cognitive testing showed a good outcome (improved or no change) in all cognitive domains. Post-surgical EEG showed new focal slowing and sharp waves. There was no change in QOL. CONCLUSION: CC can be effective in reducing GTC, absence and myoclonic seizures in patients with refractory IGE. These findings suggest that interhemispheric communication of the cerebral cortices plays an important role in the generation of seizures in IGE. Anterior CC appears safe while complete callosotomy has a risk of disconnection syndrome.