Anoxia–ischemia: A mechanism of seizure termination in ictal asystole

Cerebral anoxia–ischemia (CAI) is a potent inhibitor of cerebral hyperactivity and a potential mechanism of seizure self-termination. Prolonged ictal asystole (IA) invariably leads to CAI and has been implicated as a potential cause of sudden unexplained death in epilepsy (SUDEP). IA was seen in eight consecutive patients (0.12% of all patients monitored). Ten of their seizures with IA had evidence of CAI on electroencephalography (EEG), manifested by bilateral hypersynchronous slowing (BHS), and were compared to 18 seizures without signs of CAI. The ictal EEG pattern resolved in all 10 CAI events with onset of the BHS. The period from IA onset to seizure end was reduced in events with BHS compared to events without BHS (10.5 s vs. 28.3 s, respectively; p = 0.005), and the total seizure duration tended to be shorter. Anoxia–ischemia as a result of IA may represent an effective endogenous mechanism for seizure termination and may explain why the hearts of patients with ictal asystole reported to date in the literature resumed beating spontaneously.     

How common is ictal hypoxemia and bradycardia in children with partial complex and generalized convulsive seizures?

Purpose: Autonomic effects of seizures, including cardiorespiratory abnormalities, may be involved in sudden unexpected death in epilepsy (SUDEP). The purpose of this study was to determine the prevalence and risk factors for ictal hypoxemia (oxygen saturation <90%) and ictal bradycardia (heart rate < second percentile for age) in children during recorded seizures. Methods: The medical records of children admitted to our Epilepsy Monitoring Unit (EMU) between November 1, 2007 and March 13, 2009 were reviewed. Children selected for this study had at least one partial complex or generalized convulsive seizure with recorded oximetry and/or heart rate data. Results: Forty‐nine children were identified and 225 seizures were analyzed. Ictal hypoxemia was observed in 48.9% of children and 26.8% of seizures. Ictal hypoxemia was significantly more likely to occur during generalized versus nongeneralized seizures (43.9% vs. 18.9%) and when tapering antiepileptic drugs (AEDs) (75% vs. 35.5%). For partial complex seizures, there was an association between ictal hypoxemia and prolonged seizure duration. There was no correlation between ictal hypoxemia and partial seizure onset localization or lateralization. Ictal bradycardia occurred in 8.2% of children and 3.7% of seizures. Ictal bradycardia was observed solely with partial complex seizures of extratemporal onset. Due to the low prevalence of ictal bradycardia, these findings were not statistically significant. Discussion: Ictal hypoxemia is common, particularly in the setting of generalized tonic–clonic seizures, prolonged partial complex seizures, and when AEDs are tapered. In contrast to previous ictal bradycardia studies, ictal bradycardia occurred exclusively in extratemporal partial complex seizures in this cohort.     

Clinical cues for detecting ictal asystole

Objective The occurrence of asystole during an epileptic seizure is the most dramatic manifestation of ictal bradycardia. Recognition of ictal asystole is important as treatment with both antiepileptic drugs and cardiac pacing may be necessary. The purpose of this study was to identify clinical cues to aid in the detection of ictal asystole. Methods We analyzed the clinical and electrophysiologic features of all recorded seizures in consecutive patients diagnosed with ictal bradycardia and asystole on prolonged video-EEG/ECG monitoring over a 14 year period. Results Twenty-nine seizures with ictal bradycardia were identified in 13 patients. Of these, 11 seizures in seven patients were associated with asystole. Bilateral transient limb movements consisting of asymmetric posturing or jerking occurred during eight episodes of ictal asystole, and loss of muscle tone occurred during four. In contrast, neither bilateral limb movement nor loss of muscle tone was observed in any of the non-asystolic seizures, whether ictal bradycardia was present or not. All patients with ictal asystole reported a history of seizure-related falls and brief body and limb jerking. Conclusions The presence of loss of muscle tone or bilateral asymmetric jerky limb movements during a seizure suggests the possibility of ictal asystole. Video-EEG/ECG monitoring should be considered in patients with epilepsy demonstrating these clinical features to determine if ictal asystole is present.     

Evolution and Localization of Postictal Blood Flow Changes in Partial Seizures Demonstrated by SPECT: Use of Quantitative Difference Images

Ictal single photon emission computed tomography (SPECT) is a sensitive means of seizure localization in partial epilepsy. The purpose of this study is to enhance the diagnostic yield of postictal SPECT for epilepsy and to overcome the difficulties in its conventional interpretation. We developed a method for coregistration, normalization, and subtraction of interictal from ictal SPECT to reveal positive difference images (and ictal from interictal to reveal negative difference images) of cerebral blood flow (CBF) during seizures. This method also allows quantification of regions of greatest percent increase and decrease, normalized to seizure duration. We studied 12 patients who had confirmed epileptogenic regions by surgery and pathology (seven temporal, five extratemporal). In all 12 patients, with either early (during ictus) or late injection (after seizure termination), the difference images showed increases or decreases respectively in blood flow consistent with the epileptogenic region. We highlight the localizing value of the negative difference change in perfusion (state of hypoperfusion) that persists for up to 100 seconds after seizure termination and corresponds to the epileptogenic region. Application of this technique for the quantification of perfusion changes during seizure or immediately after seizure cessation enhances the diagnostic yield of SPECT in both temporal and extratemporal epilepsy.     

The ictal bradycardia syndrome: localization and lateralization

PURPOSE: Previous studies have established the importance of the insular cortex and temporal lobe in cardiovascular autonomic modulation. Some investigators, based on the results of cortical stimulation response, functional imaging, EEG recordings of seizures, and lesional studies, have suggested that cardiac sympathetic and parasympathetic function may be lateralized, with sympathetic representation lateralized to the right insula, and parasympathetic, to the left. These studies have suggested that ictal bradycardia is most commonly a manifestation of activation of the left temporal and insular cortex. However, the evidence for this is inconsistent. We sought to assess critically the predictable value of ictal bradycardia for seizure localization and lateralization. METHODS: In this study, we reviewed the localization of seizure activity in 13 consecutive patients with ictal bradycardia diagnosed during prolonged video-EEG monitoring at Mayo Clinic Rochester. The localization of electrographic seizure activity at seizure onset and bradycardia onset was identified in all patients. In addition, we performed a comprehensive review of the ictal bradycardia literature focusing on localization of seizure activity in ictal bradycardia cases. RESULTS: All occurrences of ictal bradycardia in the 13 identified patients were associated with temporal lobe-onset seizures. However, no consistent lateralization of seizure activity was found at onset of seizure activity or at onset of bradycardia in this population. Seizure activity was bilateral at bradycardia onset in nine of 13 patients. The results from the literature review also showed that a predominance of patients had bilateral activity at bradycardia onset; however, more of the ictal bradycardia cases from the literature had left hemispheric localization of seizure onset. CONCLUSIONS: Ictal bradycardia most often occurs in association with bilateral hemispheric seizure activity and is not a consistent lateralizing sign in localizing seizure onset. Our data do not support the existence of a strictly unilateral parasympathetic cardiomotor representation in the left hemisphere, as has been suggested.     

Ictal asystole with convulsive syncope mimicking secondary generalisation: a depth electrode study

Ictal bradycardia is rare and its localising value is debated. Bradyarrhythmias are, however, important because of their potential connection to sudden death and ability to affect clinical seizure manifestations. Cerebral hypoperfusion induces loss of consciousness, at times with myoclonic jerks, whose clinical differentiation from a generalised convulsive seizure may prove difficult.Two invasive and five surface monitored seizures recorded over two years in a 51 year old woman with post-traumatic epilepsy characterised by seizure-triggered asystole were analysed. All seven seizures showed left temporal onset. Both intracranially recorded events started in the left anterior hippocampus/amygdala, spreading to the contralateral hippocampus in 35 and 25 seconds. Within 10 seconds an electrocardiogram showed asystole lasting 21 and 28 seconds, associated with suppression of recorded cerebral electrical activity, except a polyspike suppression pattern remaining in the hippocampi. Clinically, the patient, concomitantly with the cerebral suppression, developed myoclonic twitches of the limbs. A dual chamber cardiac pacemaker was implanted; at 11 months follow up, the patient has experienced only infrequent partial seizures, with none involving falls or shaking.Left temporal lobe seizures produced convulsive syncope initiated by ictal asystole. These observations suggest that intertemporal spread is necessary, though not sufficient, to produce bradycardia and asystole. Furthermore, pacemakers may decrease seizure severity, as well as potentially protect against malignant bradyarrhythmias.     

Management and long-term outcome in patients presenting with ictal asystole or bradycardia

Purpose: Ictal asystole (IA) and ictal bradycardia (IB) are rare autonomic symptoms during epileptic seizures and may be potentially life‐threatening. Guidelines for the care of these patients are missing. The aim of this multicenter study was to evaluate the management and long‐term outcome in patients with IA and IB. Patients and Methods: All patients with IA and IB were included from four epilepsy centers (Bielefeld, Kork, Marburg, and Zürich) from 2002 until 2009. Using a standardized assessment form, clinical data, treatment decisions, and outcomes were extracted from patient charts and simultaneous electroencephalography/electrocardiography (EEG/ECG) recordings. Key Findings: Seizures with IA or IB were identified in 16 patients. In all patients an associated temporal seizure pattern was recorded and in 15 patients, sudden falls, fainting, or trauma was previously reported or recorded during the monitoring. In three patients (18.8%) diagnosis of focal epilepsy was newly established and anticonvulsive treatment was initiated. Two patients with refractory epilepsy underwent epilepsy surgery. In seven patients (43.8%) a cardiac pacemaker was implanted. In 14 of 16 treated patients, seizure freedom (n = 5) or absence of sudden falls, fainting, or trauma (n = 9) could be achieved. Two patients denied epilepsy surgery as well as a pacemaker and continue to have frequent falls and trauma. Significance: Our study demonstrates that epilepsy surgery and antiepileptic drugs may lead to sustained freedom of seizures as well as ictal syncope. In drug‐resistant patients not suitable for epilepsy surgery, implantation of a cardiac pacemaker may prevent sudden falls as well as trauma. Based on our results and previously reported cases we propose a treatment algorithm.     

Electrocardiographic and oximetric changes during partial complex and generalized seizures

Significant autonomic changes occur during seizures and may be related to sudden unexplained death in epilepsy (SUDEP). Accordingly, we performed a study to determine the prevalence of heart rate, QTc, and oximetric changes during seizures and analyzed their association with SUDEP risk factors. We analyzed 218 seizures from 76 patients. Ictal sinus tachycardia occurred in 57% of seizures and was associated with ≥3 failed AEDs (p=0.001), generalized seizures (p<0.001), and normal brain MRI (p=0.04). Ictal sinus bradycardia was rare, occurring in 2% of seizures. Ictal bradycardia was associated with seizure clustering (p=0.028) and reported history of ≥50 seizures/month (p=0.01). Depending on the correction formula utilized for calculating QTc, clinically significant ictal QTc prolongation (≥460ms for children ≤13 years, ≥470ms for males age >13, and ≥480ms for females age >13) occurred in 4.8-16.2% of seizures, while ictal QTc prolongation ≥500ms occurred in 2.9-16.2%. Ictal QTc shortening ≤340ms was observed in 3.8-4.8% of seizures. Ictal hypoxemia occurred in 25% of seizures and was associated with normal MRI (p=0.01), longer seizure duration (p=0.049), and ictal tachycardia (p=0.003). Such findings may have implications for understanding the pathogenesis of SUDEP.     

Duration of complex partial seizures: an intracranial EEG study

PURPOSE: The dynamics of partial seizures originating from neocortical and mesial temporal regions are thought to differ, yet there are no quantitative comparative studies. The studies reported here investigate the duration of complex partial seizures in these populations using analyses of seizures recorded from intracranial arrays. METHODS: Data were collected from patients undergoing presurgical evaluation with intracranial electrodes. Seizure duration was defined as the time of earliest sustained ictal activity until the termination either in all electrodes (global duration, GD), or at the onset area (focal duration, FD). Patients were divided into three groups: mesial temporal lobe epilepsy (MTLE), neocortical temporal lobe epilepsy (NCTLE), and neocortical extratemporal lobe epilepsy (NCXTLE). RESULTS: Complex partial seizure durations were significantly longer in the MTLE group compared to the NCXTLE group. Median GD for MTLE was 106 s, and for NCXTLE was 78 s. There were no significant differences between seizure durations when comparing MTLE group to NCTLE group, or comparing NCTLE group to NCXTLE group. In the MTLE group, patients with bilateral recording arrays had significantly longer median seizure durations (GD and FD) than those sampled with unilateral arrays. CONCLUSIONS: In this select group of patients there is a significant difference between the duration of complex partial seizures of mesial temporal and neocortical extratemporal origin with mesial temporal complex partial seizures being longer. This may result from a number of possibilities including the bilateral propagation of some mesial temporal seizures and differences in ictal generators of the underlying networks.     

Cardiac rhythm during temporal lobe seizures.

We studied the neuroanatomic correlates of ictal tachycardia in 27 seizures from five patients with unilateral temporal lobe epilepsy being evaluated with bilateral temporal lobe depth electrodes and orbitofrontal subdural electrodes. There were 11 complex partial seizures, three simple partial seizures, and 13 subclinical seizures. For all seizures, heart rate (HR) increased in a graded fashion as new cortical regions anywhere in the brain were recruited into the seizure. HR plateaued at the new level despite EEG frequency changes until the next region became involved. Increases in HR did not correlate with increased duration of seizures but rather with volume of brain involved. Restricted amygdaloid seizure activity was generally insufficient to alter HR. We conclude that the amygdala has a limited role in modulating HR during seizures, and ictal tachycardia depends principally on the volume of cerebral structures recruited into a seizure.     

Influence on ictal seizure semiology of rapid withdrawal of carbamazepine and valproate in monotherapy

PURPOSE: To quantify changes in ictal seizure semiology during rapid withdrawal of carbamazepine (CBZ) and valproate (VPA) from a monoregimen in presurgical evaluation. METHODS: Therapeutic intensive seizure analysis (TISA) with video-EEG monitoring was used in 33 patients with pharmacoresistant partial epilepsy undergoing complete withdrawal of CBZ (20 patients) or VPA (13 patients) from a monoregimen. Monitoring phases included a 3-day baseline phase, a 3-day rapid antiepileptic drug (AED) withdrawal phase, and another 3-day AED-free phase with AEDs in subtherapeutic levels. Seizure variables as complete processes and their various elements (ictal signs) were analyzed, including duration (seconds), intensity (on a scale of 0 to 3), frequency (number per 3 days), and total duration of seizures and ictal signs in 3 days (seconds). The localization of seizure patterns on ictal EEG recording (EEG seizure onset) and the first appearing clinical ictal phenomena (initial ictal signs) were recorded. RESULTS: A total of 188 seizures in the CBZ group and 57 seizures in the VPA group were investigated. Compared with the baseline phase, the CBZ group showed increases in duration, frequency of seizures, various ictal signs, and secondarily generalized tonic and clonic signs during the following two phases. Significantly increased values of the VPA group were observed in seizure duration and frequency of hypermotoric phenomena during the AED-free phase. More patients in the CBZ group had secondarily generalized clonic signs during the AED-free phase. EEG seizure onset and initial ictal signs showed no obvious changes between study phases. CONCLUSIONS: Withdrawal of CBZ is followed more quickly by an increase of seizure frequency and severity than is the case for VPA withdrawal. Both CBZ and VPA withdrawal influences seizure propagation rather than the seizure-onset characteristics, which speaks in favor of its use in presurgical evaluation.     

Electrocardiographic changes during electrographic seizures

The occurrence of high-risk cardiac arrhythmias during electrographic seizures has been proposed as a possible cause for sudden unexpected death in patients with epilepsy. Several anecdotal case reports have documented various cardiac irregularities during seizures. We reviewed simultaneous 24-hour electroencephalographic - electrocardiographic studies obtained by ambulatory cassette electroencephalography in 45 patients who experienced 106 electrographic seizures. An increase in heart rate was seen in 96% of seizures, while in four seizures, the rate was unchanged. Heart rate increase measured from 1 minute preictally to intraictal peak ranged from 0% to 160% (mean, 60%). The onset of tachycardia was usually within several seconds (before or after) of the seizure onset, and often persisted for several minutes after termination of the discharge. No difference was found in patients with lateralized vs generalized seizures. Neither ventricular ectopia, conduction defects, or bradycardia were observed during the ictal episodes. We conclude that ictal tachycardia is the rule during electrographic seizures, and that high-risk cardiac arrhythmias are uncommon.     

Respiratory changes with seizures in localization‐related epilepsy: Analysis of periictal hypercapnia and airflow patterns

Purpose: The rate of sudden unexpected death in epilepsy (SUDEP) approaches 9 per 1,000 patient‐years in patients with refractory epilepsy. Respiratory causes are implicated in SUDEP. We reported that ictal hypoxemia occurs in one‐third of seizures in localization‐related epilepsy. We now report on respiratory changes in the ictal/postictal period including changes in end‐tidal CO₂ (ETCO₂) that correlate directly with alveolar CO₂, allowing a precise evaluation of seizure‐related respiratory disturbances. Methods: One hundred eighty‐seven seizures were recorded in 33 patients with localization‐related epilepsy, with or without secondarily generalized convulsions, undergoing video‐electroencephalography (EEG) telemetry with recording of respiratory data. Results: The ictal/postictal ETCO₂ increase from baseline was 14 ± 11 mm Hg (11, ?1 to 50) [mean ± standard deviation (SD) (median, range)]. ETCO₂ peak was at or above 50 mm Hg with 35 of 94 seizures, 60 mm Hg with 15, and 70 mm Hg with five seizures. Eleven of the 33 patients had seizures with ETCO₂ elevation above 50 mm Hg. The duration of ictal/postictal ETCO₂ increase above baseline was 424 ± 807 s (154, 4 to 6225). The duration of ictal apnea was 49 ± 46 s (31, 6–222); most ictal apneic events were central. Oxygen desaturation to 60% or less occurred with 10 seizures, including five that did not progress to generalized convulsions. Respiratory rate and amplitude increased postictally. The peak ictal ETCO₂ change and duration of change were not associated with apnea duration or seizure duration. Peak ETCO₂ change was significantly associated with contralateral seizure spread. Conclusions: Severe and prolonged increases in ETCO₂ occur with seizures. Postictally, respiratory effort is not impaired. Ictally triggered ventilation–perfusion inequality from pulmonary shunting or transient neurogenic pulmonary edema may account for these findings.     

Lateralized seizure termination: relationship to outcome following anterior temporal lobectomy.

Determination of side of seizure onset is critical for a successful outcome following epilepsy surgery. Little is known about the significance of lateralized seizure termination. Sustained seizure activity contralateral to side of seizure onset, following termination of ictal activity ipsilateral to side of onset, may suggest the presence of an independent focus. Such activity, if present, should predict a poor outcome. We studied side of seizure termination in 13 patients undergoing monitoring with bitemporal depth electrodes and correlated this to outcome following anterior temporal lobectomy (ATL). Side of seizure onset was determined for all seizures during that evaluation. Based on side of final cessation of ictal activity, patients were classified as having ipsilateral final termination or simultaneous termination (Group 1; N=6) or contra-lateral or mixed final termination (Group 2; N=7). The Duke outcome classification system was used. At the end of 2 years follow-up, 6/6 patients in Group 1 and 3/7 patients in Group 2 were seizure free. We conclude that lateralized seizure termination during evaluation with depth electrodes may be useful in predicting outcome following ATL. Continued seizure activity contralateral to side of seizure onset (following termination of ictal activity ipsilateral to side of onset) predicts a poor outcome. This may indicate the presence of an independent seizure focus opposite to the side of surgery.     

Abruptly attenuated terminal ictal pattern in pediatrics.

PURPOSE: We examined the ictal discharges at the end of pediatric seizures and categorized the various patterns. One particular pattern, termed "abruptly attenuated termination" was studied in detail. METHODS: Ictal segments captured on video-EEG monitoring during a 26-month interval were analyzed for a variety of ictal termination patterns, including one that we rigorously defined as abruptly attenuated termination pattern (AAT). We studied the associations between AAT and the other ictal EEG and clinical features. RESULTS: AAT was noted in 16 of 200 (8%) pediatric seizures. All 16 were immediately preceded by repetitive spikes or spike-waves. The presence of AAT also correlated with ictal spread pattern, initial ictal pattern, laterality of onset, seizure duration, age, and epilepsy etiology. AAT is more often noted in children older than 6 months and in children with idiopathic or cryptogenic forms of epilepsy. CONCLUSIONS: The minority of pediatric seizures recorded in a tertiary epilepsy monitoring unit end with diffuse, synchronized abrupt attenuation. AAT probably is the result of an active process that is developmentally related. It appears to require some degree of mature and intact neurophysiology and may involve the thalamocortical circuit.     

Therapeutic intensive seizure analysis (TISA) in presurgical evaluation of Losigamone

OBJECTIVE: The new method TISA was used to evaluate Losigamone efficacy. METHODS: Sixteen patients with pharmacoresistant partial seizures undergoing presurgical evaluation were randomized in this double-blind, placebo-controlled, parallel-group Losigamone monotherapy study under continuous video-EEG monitoring. Duration (in s, of each seizure and each ictal sign), intensity (grade zero to three), N/24h (number of seizures and ictal signs per 24 h), D/24h (seconds per 24 h covered by seizures and ictal signs) and seizure free intervals were recorded. RESULTS: A total of 246 seizures were intensively analyzed. The duration and intensity of all seizures improved more in the active treatment group than in the placebo group. There was a statistically significant superiority in the duration of the seizure free interval in the Losigamone group. Ictal signs such as oro-alimentary automatisms and fumbling were improved during Losigamone treatment. CONCLUSION: Losigamone has a preferred inhibitory effect on propagated epileptic activity. TISA is a sensitive method for evaluation of the selective effects of AEDs.     

Peri-ictal heart rate variability parameters as surrogate markers of seizure severity

This study aims at defining objective parameters reflecting the severity of peri-ictal autonomic changes and their relation to post-ictal generalized electroencephalography (EEG) suppression (PGES), with the view that such changes could be detected by wearable seizure detection systems and prove useful to assess the risk of sudden unexpected death in epilepsy (SUDEP). To this purpose, we assessed peri-ictal changes in heart rate variability (HRV) and correlated them with seizure duration, intensity of electromyography-based ictal muscle activity, and presence and duration of post-ictal generalized EEG suppression (PGES). We evaluated 75 motor seizures from 40 patients, including 61 generalized tonic-clonic seizures (GTCS) and 14 other major motor seizure types. For all major motor seizures, HRV measurements demonstrated a significantly decreased parasympathetic activity and increased sympathetic activity in the post-ictal period. The post-ictal increased sympathetic activity was significantly higher for GTCS as compared with non-GTCS. The degree of peri-ictal decreased parasympathetic activity and increased sympathetic activity was associated with longer PGES (>20 s), longer seizure duration, and greater intensity of ictal muscle activity. Mean post-ictal heart rate (HR) was an independent predictor of PGES duration, seizure duration, and intensity of ictal muscle contraction. Our results indicate that peri-ictal changes in HRV are potential biomarkers of major motor seizure severity.     

Lateralization of cerebral blood flow in juvenile absence seizures

Cerebrovascular blood flow in absence seizures and flow patterns during the ictal period have not been thoroughly investigated. We aimed to evaluate cerebral blood flow changes in typical juvenile absence seizures during the ictal and postictal phases. Seizures were recorded in three patients (mean age: 21 ± 1 years) with multiple daily typical absence seizures. Simultaneous video electroencephalography and bilateral middle cerebral artery transcranial Doppler ultrasonography recordings were conducted during seizures. Basal, ictal, and postictal blood flow velocities were recorded bilaterally, and offline analyses were performed in relation with generalized spike and wave discharges. Total of 43 seizures were recorded. Ictal increase and postictal decrease of cerebral blood flow velocities were significant for both sides (P < 0.001). The interhemispheric asymmetry in the ictal velocity increase was significant (P < 0.05). The interhemispheric asymmetry in the postictal velocity decrease was not significant (P > 0.05). The blood flow velocity increase after seizure onset indicates a vascular coupling mechanism. A sudden and then a gradual decrease in blood flow velocity, which lasted even after the seizure ceased, might suggest a preventive mechanism to avoid excessive seizure duration or even an absence status epilepticus. Significant asymmetries in increase and a symmetrical decrease may support the cortical focus theory.     

Cardiac asystole during a temporal lobe seizure

The association between temporal lobe seizures and cardiac arrhythmias has been anecdotally reported in the literature. Ictal bradycardia and cardiac asystole are rare, and maybe underestimated. The physiological mechanism is poorly understood. We report a patient with left temporal lobe seizures who developed ictal bradycardia and cardiac asystole during a complex partial seizure and required a subsequent placement of a pacemaker.     

Mechanism of electrographic seizure generation in the hippocampal slice in Mg2+-free medium: the role of GABAa inhibition

We recently have described a new model of ictal-like electrographic activity in the hippocampal slice. When magnesium is eliminated from the medium bathing the hippocampal slice, spontaneously occurring electrical events which closely resemble electrographic seizures can be recorded extracellularly from area CA3. In order to begin to understand the mechanisms of initiation and termination of these seizures, the present study investigated the role of GABAa-mediated inhibition in these processes. Prior to the onset of a seizure recorded from stratum pyramidale of CA3, a twin-pulse stimulus to stratum radiatum of CA3 evoked twin EPSPs. Following the seizure, the same stimulation triggered a strong epileptiform burst. This is consistent with the known reduction of GABAa inhibition after seizures in vivo. Addition of bicuculline, picrotoxin, or penicillin, which reduce the efficacy of GABAa-mediated inhibition in this system, caused triggered epileptiform bursting to occur prior to the seizure as well. They also lowered the threshold for the production of seizures, facilitating their spontaneous occurrence or elicitation by fewer stimulus pulses. This suggests that the GABAa inhibition present in magnesium-free (0-Mg) plus baclofen medium tends to suppress the onset of seizures and raises the seizure threshold. However, these drugs did not prolong the ictal events. This suggests that in this model, GABAa-mediated inhibition is not responsible for termination of the seizure-like activity. Although there is some potentiation of the tonic firing phase of the seizures under these conditions, there is no gross change in the morphology of the events when inhibition is suppressed. In this model, therefore, GABAa-mediated inhibition plays a limited role in determining the structure and duration of the ictal events, but may contribute to the seizure threshold.