The EEG Findings in Extratemporal Seizures

Summary: Extratemporal seizures originate from the frontal, central, parietal, occipital, and midline regions of the brain. The scalp EEG can show various types of interictal and ictal discharges consisting of spikes, spike and wave sharp waves, paroxysmal fast activity, or rhythmic activity in the β, α, θ, or δ frequency ranges. The discharges can occur as focal, regional, lateralized, or secondarily generalized discharges. Discharges arising from the frontal region are varied and at times complex. Centro-temporal spikes associated with benign epilepsy of childhood have a characteristic blunt spike and wave appearance. Centro-parietal spikes can occur in children with benign childhood epilepsy or in association with symptomatic epilepsies at any age. Occipital spike discharges have been seen in young children with visual problems, benign occipital epilepsy of childhood, the Sturge-Weber syndrome, and other symptomatic or structural lesions involving the occipital lobe. There may be problems with detection of the source of origin of seizures secondary to the anatomy of the various regions, deep foci, small restricted foci, rapid spread of epileptiform discharges, and contaminating effects of muscle and movement artifact. Depth or intracranial recordings may help in further localization of foci.     

Interictal Spiking Increases with Sleep Depth in Temporal Lobe Epilepsy

Summary: Purpose : To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy.
Methods: At the time of study, subjects were seizure-free for 224 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2).
Results: The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal.
Conclusions: Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.     

Prediction of Surgical Outcome by Interictal Epileptiform Abnormalities During Intracranial EEG Monitoring in Patients with Extrahippocampal Seizures

PURPOSE: Ictal intracranial EEG recordings obtained during continuous preoperative monitoring are often used to localize the region of seizure onset for purposes of surgical resection in patients with extrahippocampal seizures. Whether interictal epileptiform abnormalities during long-term monitoring can predict surgical outcome in this group is not established. METHODS: Intracranial EEGs of patients who underwent extrahippocampal resective epilepsy surgery were reviewed for interictal epileptiform abnormalities before medication discontinuation or first seizure occurrence. Interictal abnormalities were categorized as within or beyond the confines of surgical resection. We correlated these findings with the region of seizure onset, the pathologic substrate, and surgical outcome (by using Engel criteria) at 1-year minimum follow-up. RESULTS: Of 13 patients with interictal epileptiform abnormalities, six patients had interictal epileptiform discharges extending beyond the confines of surgical resection. These patients all had poor surgical outcome even if the region of electrographic seizure onset was resected. Seven patients had focal interictal epileptiform discharges, the entire extent of which were resected. All had good outcomes. All patients with structural lesions had focal interictal epileptiform abnormalities and good surgical outcomes. The spatial extent of interictal epileptiform discharges varied among patients with nonstructural lesions. However, those whose regions of interictal epileptiform abnormality were included in surgical resection also had good surgical outcome. CONCLUSIONS: The presence of interictal epileptiform discharges extending beyond the area of resection correlates with poor surgical outcome in patients with extrahippocampal epilepsy. In contrast, patients with focal interictal epileptiform discharges included in surgical resection have good surgical outcomes.     

Interictal Spikes and Hippocampal Somatostatin Levels in Temporal Lobe Epilepsy

We investigated the relationship between somatostatin-like immunoreactivity (SSLI) and interictal spikes (IIS) in human temporal lobe epileptic tissue. IIS counted manually from depth electrode recordings obtained preoperatively were expressed as spike frequency in anterior, middle, and posterior portions of hippocampus. SSLI was determined by radioimmunoassay (RIA). An inverse relationship between SSLI in the entorhinal cortex (EC) and IIS frequency in hippocampus was present (r = -0.55, p = 0.06). No correlation between IIS and SSLI in CA4, CA3, CA1, or the dentate was evident. This finding suggests a role of the EC in generation, regulation, or expression of interictal paroxysmal electrical activity in temporal lobe epilepsy (TLE), for which somatostatin may be a marker.     

Interictal Epileptiform Discharges in Temporal Lobe Epilepsy Due to Hippocampal Sclerosis Versus Medial Temporal Lobe Tumors

PURPOSE: It remains controversial whether a specific pattern of interictal epileptiform activity exists that may help to differentiate temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) from other forms of TLE. In this study, we characterized the distribution of interictal epileptiform discharges in TLE due to HS as compared with those in patients with tumors restricted to the medial temporal lobe structures. METHODS: The study included 21 adult patients with unilateral HS who remained seizure free (>1 year) after anterior temporal lobectomy with amygdalohippocampectomy. Patients with "dual pathology" were excluded. The comparison group consisted of nine patients with tumors restricted to the amygdala and hippocampus. All patients underwent video-EEG monitoring preoperatively by using 39 scalp electrodes (including the 10-10 system over both temporal regions) and bilateral sphenoidal electrodes. RESULTS: The HS patient group showed a significantly higher percentage of ipsilateral epileptiform discharges maximal at anterior temporal electrodes (median, 97.0%; sphenoidal electrode alone, 88.1%), as compared with the tumor group (median, 72.1%; p<0.001; sphenoidal electrode alone, 24.8%; p<0.001). The HS group had significantly fewer extratemporal spikes/sharp waves (median, 0.0), as compared with the tumor group (10.0%; p<0.001). At least 90% of the interictal discharges were located in the anterior temporal region in 20 (95.2%) of 21 HS patients, but in none of the tumor patients (p<0.001). Bilateral temporal discharges were found in nine (42.9%) of 21 patients with HS and in two (22.2%) of nine tumor patients (p = 0.42). CONCLUSIONS: We conclude that ipsilateral interictal epileptiform discharges outside the anterior temporal region are rare (<10%) in adults with intractable TLE due to unilateral HS. Frequent posterior or extratemporal sharp waves may detract from the certainty of this diagnosis in complicated cases. These restricted epileptiform discharges suggest a smaller irritative zone in HS as compared with medial tumors, or a more organized activity associated with intrinsic hippocampal disease. Bilateral epileptiform discharges were not uncommon in both groups.     

Interictal epileptiform discharges vary across age groups

ObjectiveTo investigate whether the occurrence and morphology of interictal epileptiform discharges (IEDs) in scalp-EEG change by age.Methods10,547 patients who had a standard or sleep deprived EEG recording reported using the SCORE standard were included. 875 patients had at least one EEG with focal IEDs. Focal IED morphology was analyzed by age using quantitative measures in EEGLAB and by visual classification based on the SCORE standard. We present distributions of IED measures by age group, with medians, interquartiles, 5th and 95th percentiles.ResultsFocal IEDs occurred most frequently in children and elderly. IED morphology and localization depended on age (p < 0.001). IEDs had higher amplitudes, sharper peaks, larger slopes, shorter durations, larger slow-wave areas and wider distributions in children. These morphological characteristics diminished and the IEDs became more lateralized with increasing age. Spike asymmetry was stable across all age groups.ConclusionsIEDs have age-dependent characteristics. A spike detector, human or computer, should not operate with the same set of thresholds for patients at various age. With increasing age, focal IEDs are less sharp, have lower amplitudes, have less prominent slow-waves and they become more lateralized. Our findings can help EEG readers in detecting and correctly describing IEDs in patients of various age.SignificanceEEG readers should always consider patient age when interpreting interictal epileptiform discharges.     

Suppression of Interictal Spikes and Seizures by Stimulation of the Vagus Nerve

The effects of electrical stimulation of the vagus nerve, a proposed treatment for patients with intractable epilepsy, on focal interictal spikes produced by penicillin and EEG secondarily generalized seizures induced by pentylenetetrazol were assessed in rats. Interictal spike frequency was reduced by 33% during 20 s of stimulation (p < 0.001) and remained low for ≤3 min. Amplitude of residual spikes was also decreased. Cardiac and respiratory rates were suppressed. Cooling the nerve proximal to the point of stimulation abolished the EEG and respiratory effects. A similar reduction in spike frequency of 39% was obtained by heating the animals' tail (p < 0.01). Vagal stimulation at onset of seizures reduced mean seizure duration from 30.2 ± 15.7 s without stimulation to 5.0 ± 1.8 s (p < 0.01). Only the EEG equivalent of the clonic phase of the seizure was affected. These findings suggest that vagus nerve stimulation can be a potent but nonspecific method to reduce cortical epileptiform activity, probably through an indirect effect mediated by the reticular activating system.     

The Functional Organization of the Interictal Spike Complex in Benign Rolandic Epilepsy

Summary: Purpose : We studied the functional organization of the interictal epileptic spike complex in patients with benign rolandic epilepsy of childhood (BREC).
Methods : We recorded interictal epileptiform spikes and somatosensory evoked potentials after median nerve stimulation, providing a biologic marker for the location of the central sulcus in 12 patients with BREC. We used multiple dipole modeling to assess the number, the three-dimensional intracerebral location, and the time activity of the underlying neuronal sources.
Results : Although the interictal spike complex could be modeled by a single tangential dipolar source in seven patients (group 1), in the remaining five patients, two sources—a radial and a tangential dipole—were necessary adequately to explain the interictal spikes (group 2). The tangential source was located deeper than the radial source and was characterized by a frontal positivity and a centroparietal negativity with a phase reversal across the central sulcus, suggesting that the interictal spikes originated in the anterior wall of the central sulcus. The radial source showed a single electronegativity over the ipsilateral central region, which would be compatible with involvement of the top of either the pre- or postcentral gyrus. Both sources showed biphasic time patterns with an average latency difference of 30 ms.
Conclusions : Our results indicate that in some patients with typical BREC, the interictal epileptiform spike complex is generated by multiple, simultaneously active neuronal populations within the central region and that epileptiform activity is propagated between these two adjacent cortical areas.     

Ictal Behaviors During Nonepileptic Seizures Differ in Patients with Temporal Lobe Interictal Epileptiform EEG Activity and Patients Without Interictal Epileptiform EEG Abnormalities

Summary: Purpose: Ictal behaviors during psychogenic non-epileptic seizures (NES) vary considerably among individuals, and can closely resemble common semiologies of epileptic seizures (ES). We tested the hypothesis that behaviors during NES in patients who have temporal spikes would more closely resemble behaviors during ES in patients with temporal lobe epilepsy than would behaviors during NES in patients who do not have EEG spikes.
Methods: We identified 20 patients who had interictal temporal EEG spikes and EEG-video recorded NES (Study Group), 133 patients with temporal EEG spikes and recorded ES, without NES (Epileptic Group), and 24 patients with recorded NES and no epileptiform EEG abnormalities, without ES (Nonepileptic Group).
Results: The hypothesis was supported with regard to ictal motor behaviors. Motionless staring or complex automatisms occurred mainly during NES in the Study Group and during ES in the Epileptic Group. In contrast, convulsive movements or flaccid falls were most common during NES in the Nonepileptic Group. Duration of unresponsiveness was longer, and there were fewer postictal states in NES both in the Study and Non-epileptic Groups. Unresponsiveness was briefer and postictal states were more consistent in ES in the Epileptic Group, however.
Conclusions: Stereotyped motor activities during NES presumably represent learned behaviors. Processes underlying acquisition of ictal behaviors of NES probably differ in patients with interictal epileptiform EEG abnormalities compared to those without. Prior experiences and temporal lobe dysfunctions that are associated with epilepsy, and psychological characteristics that are unrelated to interictal epileptic dysfunctions, may determine ictal behaviors during NES.     

Effect of Interictal Epileptiform Discharges on Nocturnal Plasma Prolactin Concentrations in Epileptic Patients with Complex Partial Seizures

To investigate the effect of interictal epileptiform discharges (IEDs) on plasma prolactin (PRL) level, we studied 18 epileptic patients with complex partial seizures (CPS) who did not experience clinical or subclinical ictal events during all-night monitoring with polygraphic recording and video imaging. The density of IEDs peaked during non-REM stages and was significantly reduced during REM stage. Mean plasma PRL concentrations in epileptic patients, when sampled at 30-min intervals, showed a moderate but significant elevation during non-REM (p less than 0.001) and awake stages (p less than 0.005), but not during REM stage, when compared with 10 nonepileptic control subjects studied in a similar fashion. The data obtained in this physiologically controlled environment indicate that the cumulative effect of IEDs may modify PRL regulatory mechanisms, resulting in a modest elevation of plasma concentrations independent of ictal discharges.     

Interictal spikes on intracranial recording: behavior, physiology, and implications

Purpose: The physiological, pathological, and clinical meaning of interictal spikes (IISs) remains controversial. We systematically analyzed the frequency, occurrence, and distribution of IISs recorded from multiple intracranial electrodes in 34 refractory epileptic patients with respect to seizures and antiepileptic drug (AED) changes. Methods: Continuous spike counts from all recorded contacts of all implanted electrodes, and also separately for the subset of contacts involved at seizure onset, were tabulated for every hour of every day of recording, and expressed as spikes per hour in six preselected, 24‐h intervals (defined to exclude seizures): (1) on medications; (2) prepreseizure; (3) preseizure; (4) postseizure; (5) off meds; and (6) resumed meds. Mean spike rates were analyzed for differences between designated 24‐h intervals. Results: Spike rate in all recorded contacts consistently and significantly decreased after AED withdrawal, despite variability in initial spike rate, diurnal occurrence, seizure character/number/localization of onset, and type(s) of AED continued or withdrawn (p < 0.0001). A significant increase in spike rate was noted in the 24  h after seizures of medial temporal origin, in the medial temporal lobe contacts; neocortical onset seizures did not show any increase. Conclusions: These observations confirm and extend previous reports, suggesting a general effect of AED withdrawal, and a more specific effect of medial temporal lobe seizures, on IIS rate. AED mechanisms and efficacy might be demonstrated by quantifying IIS with changes in AEDs. Furthermore, variability in IIS rate after seizures distinguishes localization of seizure onset in medial temporal versus neocortical locations.     

Clinical Usefulness of the Dipole Tracing Method for Localizing Interictal Spikes in Partial Epilepsy

Summary: Purpose: To clarify the clinical usefulness of the dipole tracing method in evaluation of interictal EEG spikes in patients with partial epilepsy.
Methods : Eight patients with partial epilepsy were studied. We compared the generator source of interictal spikes detected by the dipole tracing method with the results of magnetic resonance imaging (MRI), interictayictal measurement of cerebral blood flow (CBF) by single photon emission computed tomography (SPECT), interictal measurement of glucose metabolism by positron emission tomography (PET) and invasive electrocorticogram (ECoG).
Results : In 5 patients with mesial temporal lobe epilepsy (TLE), including 3 patients who underwent standard temporal lobectomy, the dipole tracing method showed results consistent with those of other examinations and better correlation with ECoG than with other noninvasive examinations. In a patient with mesial TLE who had defects in the skull due to previous surgery, the dipoles were located more laterally than expected. In a patient with frontal lobe epilepsy (FLE) who was finally proved to have an epileptogenic area in the lateral frontal area, the spike dipoles were identified in the medial side of the frontal lobe.
Conclusions : The dipole tracing method used in the present study is useful for localizing epileptogenic areas in patients with mesial TLE. However, in patients with partial skull defects and in those with FLE, the reliability of this method is still in accuracy of the lobe level.     

Interictal EEG abnormalities in patients with psychogenic nonepileptic seizures

PURPOSE: To examine interictal EEG abnormalities in patients with psychogenic nonepileptic seizures (PNESs). METHODS: (a) Retrospective study of EEG reports of 187 consecutive patients with PNES seen at the Department of Epileptology, Bonn, Germany; (b) Blinded, multirater comparison of EEGs of all PNES patients with no other clinically recognizable cause of EEG disturbance (n = 50) and healthy controls (n = 50). RESULTS: Of 187 consecutive patients with PNESs, 57 patients had PNESs and epilepsy (PNES+E), and 130 patients, PNESs alone. The diagnosis of additional epilepsy was based on ictal (video-) EEG or on the critical assessment of all clinical data by an experienced epileptologist. Retrospective review of all available EEG reports showed that 92.9% of patients in the PNES+E and 53.8% in the PNES-only group had one or more abnormal EEGs (median number of EEGs per patient, three; range, one to 42). In the PNES-only group, EEG changes were nonspecific in 42.3% of patients. Only 50 of 130 patients with PNESs alone had no other clinically recognizable cause of EEG disturbance and entered the controlled study. In this study, 18% of patients and 10% of controls had abnormal EEGs. The frequency of epileptiform EEG changes was similar to that in previous population studies in both groups (2.0%). CONCLUSIONS: PNESs often occur in patients with organic brain disease. Even in patients with PNESs alone and no clinically recognizable cause of EEG disturbance, nonspecific abnormalities are found 1.8 times as often as in healthy controls. Interictal EEG changes are common in patients with PNESs and, in isolation, should not be interpreted as evidence of epilepsy.     

Effects of two different cycles of vagus nerve stimulation on interictal epileptiform discharges

PURPOSE: To evaluate the effects of two cycles of vagus nerve stimulation (VNS), 30 s/5 min and 7 s/18 s on the interictal epileptiform discharges (IEDs). METHODS: Twenty patients were studied, 12 with generalized and 8 with partial seizures. An EEG of 120 channels was performed during 3 different conditions, each one lasting 30 min: basal state (BS), 30 s/5 min and 7 s/18 s VNS cycles. The number and duration of IEDs, time of IEDs in 1 min (TIEDM), IEDs/NIEDs index and the spike-free period (SFP) were determined. RESULTS: In 16 patients (80%), IED decreased during 30 s/5 min cycle (Group 1) and increased in 4 (Group 2). In Group 1, during the 30 s/5 min cycle the following variables showed a decrease: TIEDM, from 12.64 s to 9.62 s (p=0.001); IED/NIED index, from 0.53 to 0.31 (p=0.021), and IED duration, from 1.57 s to 1.05 s (p=0.015); whereas SFP duration increased from 20.06 s to 37.73 s (p=0.008). The decrease in IED was 41% and the increase in SFP 88%. In the 7s/18s cycle, only SFP had an increase, 72% (p<0.043). In Group 2, an increase in IED during both cycles was found. In the 30 s/5 min cycle, TIEDM increased 56% (p=0.042) and IED/NIED index 259% (p=0.040). CONCLUSION: VNS modifies IED in an acute form, in 80% of patients the 30 s/5 min cycle decreases the epileptiform activity and it is not modified by 7 s/18 s cycle. In 20% of patients, both cycles increase the epileptiform activity.     

Interictal epileptiform discharge characteristics underlying expert interrater agreement

Objective

The presence of interictal epileptiform discharges (IED) in the electroencephalogram (EEG) is a key finding in the medical workup of a patient with suspected epilepsy. However, inter-rater agreement (IRA) regarding the presence of IED is imperfect, leading to incorrect and delayed diagnoses. An improved understanding of which IED attributes mediate expert IRA might help in developing automatic methods for IED detection able to emulate the abilities of experts. Therefore, using a set of IED scored by a large number of experts, we set out to determine which attributes of IED predict expert agreement regarding the presence of IED.

Recording Small Sharp Spikes with Depth Electroencephalography

Two patients with intractable seizures and focal temporal sharp waves also had small sharp spikes as incidental findings in their scalp electroencephalograms. Depth electroencephalography verified the intracerebral origin of the small sharp spikes and differentiated them from the more significant epileptiform abnormalities.     

Interictal EEG and the Diagnosis of Epilepsy

Summary:  The interictal EEG provides information that aids in diagnosis and management of epilepsy. One must remember that the EEG is merely a tool, and its usefulness depends largely upon the skill of the individual who wields it. Like all diagnostic tests, it has significant limitations and cannot substitute for a careful history and exercise of good judgment. Nonetheless, in skilled hands, it provides unique and vital information in many patients, and enhances our understanding of their condition.