Rhythmic Epileptiform Discharges Research Articles

Normal variants and artifacts: importance in EEG interpretation.

Overinterpretation of EEG is an important contributor to the misdiagnosis of epilepsy. For the EEG to have a high diagnostic value and high specificity, it is critical to recognize waveforms that can be mistaken for abnormal patterns. This article describes artifacts, normal rhythms, and normal patterns that are prone to being misinterpreted as abnormal. Artifacts are potentials generated outside the brain. They are divided into physiologic and extraphysiologic. Physiologic artifacts arise from the body, and include EMG, eyes, various movements, EKG, pulse, and sweat. Some physiologic artifacts can be useful for interpretation such as EMG and eye movements. Extraphysiologic artifacts arise from outside the body, and in turn can be divided into the environments (electrodes, equipment, cellphones) and devices within the body (pacemakers, neurostimulators) Normal rhythms can be divided into awake patterns (alpha rhythm and its variants, mu rhythm, lambda waves, posterior slow waves of youth, HV-induced slowing, photic driving, photomyogenic response) and sleep patterns (POSTS, vertex waves, spindles, K complexes, sleep-related hypersynchrony, frontal arousal rhythm). Breach can affect both awake and sleep rhythms. Normal variants or variants of uncertain clinical significance include variants that may have been considered abnormal in the early days of EEG but are now considered normal. These include wicket spikes and wicket rhythms (the most common normal pattern over-read as epileptiform), small sharp spikes (aka benign epileptiform transients of sleep), rhythmic midtemporal theta of drowsiness (aka psychomotor variant), Cigánek rhythm (aka midline theta), 6 Hz phantom spike-wave, 14&6 Hz positive spikes, subclinical rhythmic epileptiform discharges of adults (SREDA), slow fused transients, occipital spikes of blindness, and temporal slowing of the elderly. Correctly identifying artifacts and normal patterns can help avoid overinterpretation and misdiagnosis. This is an educational review paper addressing a learning objective of the International League Against Epilepsy (ILAE) curriculum.

Paradoxical effects of levetiracetam in people with epilepsy with rhythmic epileptiform discharges

ObjectiveTo elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects. MethodsWe examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors. ResultsIn total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01–28.21) were independently associated with paradoxical LEV effects. ConclusionsParadoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.

Volume-transmitted GABA waves pace epileptiform rhythms in the hippocampal network

Mechanisms that entrain and pace rhythmic epileptiform discharges remain debated. Traditionally, the quest to understand them has focused on interneuronal networks driven by synaptic GABAergic connections. However, synchronized interneuronal discharges could also trigger the transient elevations of extracellular GABA across the tissue volume, thus raising tonic conductance (Gtonic) of synaptic and extrasynaptic GABA receptors in multiple cells. Here, we monitor extracellular GABA in hippocampal slices using patch-clamp GABA "sniffer" and a novel optical GABA sensor, showing that periodic epileptiform discharges are preceded by transient, region-wide waves of extracellular GABA. Neural network simulations that incorporate volume-transmitted GABA signals point to a cycle of GABA-driven network inhibition and disinhibition underpinning this relationship. We test and validate this hypothesis using simultaneous patch-clamp recordings from multiple neurons and selective optogenetic stimulation of fast-spiking interneurons. Critically, reducing GABA uptake in order to decelerate extracellular GABA fluctuations-without affecting synaptic GABAergic transmission or resting GABA levels-slows down rhythmic activity. Our findings thus unveil a key role of extrasynaptic, volume-transmitted GABA in pacing regenerative rhythmic activity in brain networks.

Interictal pattern on scalp electroencephalogram predicts excellent surgical outcome of epilepsy caused by focal cortical dysplasia.

ObjectiveFocal cortical dysplasia (FCD) represents an essential cause of drug‐resistant epilepsy with surgery as an effective treatment option. This study aimed to identify the important predictors of favorable surgical outcomes and the impact of the interictal scalp electroencephalogram (EEG) patterns in predicting postsurgical seizure outcomes.MethodsWe retrospectively evaluated 210 consecutive patients between 2015 and 2019. They were diagnosed with FCD by pathology, underwent resection, and had at least one year of postsurgical follow‐up. Predictors of seizure freedom were analyzed.ResultsBased on the information at the latest follow‐up, seizure outcome was classified as Engel Class I (seizure‐free) in 81.4% and Engel Class II‐IV (non‐seizure‐free) in 18.6% of patients. There were 43, 105, and 62 cases of FCD type I, type II, and type III, respectively. The interictal EEG showed a repetitive discharge pattern (REDP) in 87 (41.4%) patients, polyspike discharge pattern (PDP) in 41 (19.5%), and the coexistence of REDP and PDP in the same location in 32 (15.2%) patients. The analyzed patterns in order of frequency were repetitive discharges lasting 5 seconds or more (32.4%); polyspikes (16.7%); RED type 1 (11.4%); continuous epileptiform discharges occupying >80% of the recording (11.4%); RED type 2 (6.2%); brushes (3.3%); focal, fast, continuous spikes (2.4%); focal fast rhythmic epileptiform discharges (1.43%); and frequent rhythmic bursting epileptiform activity (1.4%). The coexistence of REDP and PDP in the same location on scalp EEG and complete resection of the assumed epileptogenic zone (EZ) was independently associated with favorable postsurgical prognosis.SignificanceResective epilepsy surgery for intractable epilepsy caused by FCD has favorable outcomes. Interictal scalp EEG patterns were revealed to be predictive of excellent surgical outcomes and may help clinical decision‐making and enable better presurgical evaluation.

Induction of Tertiary Phase Epileptiform Discharges after Postasphyxial Infusion of a Toll-Like Receptor 7 Agonist in Preterm Fetal Sheep.

Background: Toll-like receptor (TLR) agonists are key immunomodulatory factors that can markedly ameliorate or exacerbate hypoxic–ischemic brain injury. We recently demonstrated that central infusion of the TLR7 agonist Gardiquimod (GDQ) following asphyxia was highly neuroprotective after 3 days but not 7 days of recovery. We hypothesize that this apparent transient neuroprotection is associated with modulation of seizure-genic processes and hemodynamic control. Methods: Fetuses received sham asphyxia or asphyxia induced by umbilical cord occlusion (20.9 ± 0.5 min) and were monitored continuously for 7 days. GDQ 3.34 mg or vehicle were infused intracerebroventricularly from 1 to 4 h after asphyxia. Results: GDQ infusion was associated with sustained moderate hypertension that resolved after 72 h recovery. Electrophysiologically, GDQ infusion was associated with reduced number and burden of postasphyxial seizures in the first 18 h of recovery (p < 0.05). Subsequently, GDQ was associated with induction of slow rhythmic epileptiform discharges (EDs) from 72 to 96 h of recovery (p < 0.05 vs asphyxia + vehicle). The total burden of EDs was associated with reduced numbers of neurons in the caudate nucleus (r2 = 0.61, p < 0.05) and CA1/2 hippocampal region (r2 = 0.66, p < 0.05). Conclusion: These data demonstrate that TLR7 activation by GDQ modulated blood pressure and suppressed seizures in the early phase of postasphyxial recovery, with subsequent prolonged induction of epileptiform activity. Speculatively, this may reflect delayed loss of early protection or contribute to differential neuronal survival in subcortical regions.

Prevalence of benign epileptiform variants from an EEG laboratory in India and frequency of their misinterpretation

ObjectiveTo prospectively study the prevalence of benign epileptiform variants (BEVs) and their impact on epilepsy misdiagnosis. MethodsConsecutive patients, older than one year, who underwent EEG from January 2016 to December 2019 were prospectively studied for the presence of BEVs. We used descriptions of Klass and Westmoreland (1985) to categorize the BEVs. We reviewed old EEG reports and records in patients with BEV to determine whether they were interpreted as abnormal. ResultsOf the 1862 subjects included, 1474 (79 %) patients had epilepsy while 388 (21 %) had other diagnoses. The mean age of the subjects was 23.1 ± 15.3 years and 1111 (60 %) were males. BEVs were noted in 223 (12 %) subjects undergoing EEG. The most common BEVs were wicket waves (n = 127, 6.8 %) and small sharp spikes (n = 69, 3.7 %) while 6 Hz spike-wave discharges (0.9 %), 14 and 6 Hz positive spikes (0.6 %), rhythmic mid-temporal theta burst of drowsiness (0.4 %) and subclinical rhythmic epileptiform discharges in adults (0.2 %) were less common. Patients with BEVs were older and were more likely to have normal EEG (68.2 % vs. 55.8 %; p < 0.001). BEVs were not mentioned in any of the 282 previous EEG reports. BEVS were considered to be over-interpreted as epileptiform abnormalities in 31 of 101 (30 %) records available for review. ConclusionBEVs are present in 12 % of subjects undergoing EEG. BEVS are largely unrecognized and are misdiagnosed as epileptiform discharges in one third of the patients by the general neurologists.

An Investigation into the Correlation of Scalp Electrophysiological Findings with Preoperative Clinical and Imaging Findings in Patients with Focal Cortical Dysplasia.

To evaluate the patients who had epilepsy surgery and pathologically proven focal cortical dysplasia (FCD) in order to further classify and discuss electroencephalography (EEG) findings in different pathological subtypes. This study included 19 refractory epilepsy patients who underwent surgery between 1999 and 2017 in the Istanbul Faculty of Medicine. Demographic data, preoperative examinations, scalp video EEGs, and postoperative outcomes were evaluated retrospectively. In this study, 36.8% of the patients were female. The mean age was 21.89 ± 14.64 years. Rhythmic epileptiform discharges (RED) were observed in 31.6%. 37.5% of the patients with isolated intermittent spike/sharp waves were type I, 50% were type II, and 12.5% were type III. 100% of the patients with normal background activity were FCD type II. 67% of the patients with asymmetric slowing were FCD type I, 22% was FCD type II, 11% were FCD type III. 71% of the patients with symmetrical slowing were FCD type I, 29% were FCD type II. One patient had Frontal Intermittent Rhythmic Activity, one patient had Electrical Status Epilepticus in Slow Sleep, two patients had "burst suppression," and one patient had a "switch of" sign. The frequency of focal epileptogenic activity was higher when there was an FCD lesion on magnetic resonance imaging. The findings obtained in this study did not reveal any distinctive electrophysiological features in FCD and subgroups of FCD. The incidence of REDs did not differ between types. The frequency of isolated intermittent sharp/spike waves was higher in type II than I. Intermittent and continuous EEG slowing was more commonly seen among FCD Type I patients.

Afterdischarges elicited by cortical electric stimulation in humans: When do they occur and what do they mean?

IntroductionAfterdischarges (ADs) are a common and unwanted byproduct of direct cortical stimulation during invasive electroencephalography (EEG) recordings. Brief pulse stimulation (BPS) can sometimes terminate ADs. This study investigated AD characteristics and their relevance for emergence of stimulation seizures. In addition, AD response to BPS was analyzed. Material and methodsInvasive EEG recordings including mapping with direct cortical stimulation in patients with refractory epilepsy at the Erlangen Epilepsy Center were retrospectively reviewed. Afterdischarge defined as stimulation-induced rhythmic epileptiform discharges of more than a two-second duration were analyzed regarding incidence, localization, duration, propagation pattern, morphology, and seizure emergence. In addition, the influence of AD characteristics and stimulation settings on BPS success rate was studied. ResultsA number of 4261 stimulation trials in 20 patients were investigated. Afterdischarge occurred in 518 trials (14.2%) and lasted 12.4 s (standard deviation [SD]: 8.6 s) on average. We elicited ADs in the seizure onset zone (SOZ) (n = 64; 19.4%), the irritative zone (n = 105, 20.0%), and outside the irritative area (n = 222, 12.5%). Rhythmic spikes (30.5%) and spike–wave complexes (30.3%) represented predominant morphologies. Afterdischarge morphology in the SOZ and hippocampus differed from other areas with polyspikes and sequential spikes being the most common types there (p = 0.0005; p < 0.0001 respectively). Hippocampal ADs were particularly frequent (n = 50, 38.2%) and long-lasting (mean: 16.6, SD: 8.3 s). Brief pulse stimulation was applied in 18.1% of the AD trials (n = 94) and was successful in 37.4% (n = 40). Success rates were highest when BPS was delivered within 9.5 s (p = 0.0048) and in ADs of spike–wave morphology (p = 0.0004). Fifteen clinical seizures emerged from ADs (3.55%), mostly evolving from sequential spikes. Afterdischarges in patients with stimulation seizures appeared more widespread (p < 0.0001) and lasted longer (mean duration 7.0 s) than in those without (mean duration 21.0 s, p = 0.0054). ConclusionAfterdischarges appear in the epileptogenic and nonepileptogenic cortex. Duration and propagation patterns can help to quantify the risk of stimulation seizures, with sequential spikes being most susceptible to seizure elucidation. The hippocampus is highly sensitive to AD release. Brief pulse stimulation is a safe and efficacious way to terminate ADs, especially when delivered quickly after AD onset.

Scalp electroencephalographic biomarkers in epilepsy patients with focal cortical dysplasia

To assess scalp electroencephalographic (EEG) patterns as possible biomarkers for an underlying focal cortical dysplasia (FCD) in patients with structural epilepsy. Scalp electroencephalograms (EEGs) of epilepsy patients with histologically confirmed diagnosis of FCD type I or II (n = 71, age = 3-66 years, 28 female) and of controls with other underlying pathologies (n = 43, age = 2-60 years, 16 female) were retrospectively evaluated regarding the presence or absence of 12 scalp EEG patterns previously reported to be associated with FCD. Furthermore, 2 subgroups of these biomarkers with common characteristics were also analyzed. Each of the 12 biomarkers was tested for association with FCD by comparing the presence of each feature in FCD patients and controls using Fisher exact test. A significant association with FCD as underlying etiology was found for 6 of 12 previously reported biomarkers. With decreasing odds ratios, these were continuous epileptiform discharges, 2 types of rhythmic epileptiform discharges, polyspikes, frequent rhythmic bursting epileptiform activity, and repetitive discharges as well as the subgroups containing repetitive activity and polyspikes, respectively. Presence of EEG biomarkers was independent of a visible underlying magnetic resonance imaging-visible lesion, and had similar prevalence with FCD I and II. Individual biomarkers had specificities of 65 to 98% and sensitivities of 17 to 61% for an underlying FCD, and combinations of EEG biomarkers achieved 100% specificity. This study confirms that there are several surface EEG biomarkers significantly associated with an underlying cortical dysplasia. These biomarkers may aid in localizing suspicious brain regions and provide evidence for dysplastic brain tissue also in nonlesional patients of either histological FCD subtype. Ann Neurol 2018;84:564-575.

Multimodal presurgical evaluation in children with focal cortical dysplasia

WCN 2013 No: 1499 Topic: 1 — Epilepsy Pharmacologic and genetic aspects of resistant epilepsy in children in Uzbekistan N.M. Tuychibaeva, M.I. Sigatullina, A.V. Prokhorova. Tashkent Medical Academy, Uzbekistan; Tashkent Institute of Postgraduate of Medical Education, Tashkent, Uzbekistan Objectives: To develop methods of detection for the frequency and influence of polymorphism of cytochrome Р450 genes on pharmacologic and genetic action of antiepileptic drugs (AED). Identify the role of these genetic markers in individual responses to AED and development of pharmacologic resistance in epileptic patients. Material and methods: The research is based on studying the results of treatment of patients (n= 20)with resistant epilepsy. The control group included 25 volunteers of Uzbek nationality adjusted by sex and age. Results and conclusions: 1. Minimum level of gene variety of marker CYP2C9 in children was determined with not very high frequency of heterozygosis. Reduction of frequency of heterozygote genotype, absence of adverse genotype Т/Т and simultaneous increase in the share of individuals with normal homozygous С/С genotype among apparently healthy patients can be related to selective advantage of C allele. 2. Frequency of CYP2C9 polymorphism in pharmacoresistant patients considerably exceeded that in the control group indicating the association between development of resistance to AED and the genetic marker. The obtained statistically insignificant difference is most likely caused by the small amount of patients in the groups. 3. The genotypic variant distribution analysis of polymorphic marker 9896 C-G of CYP2E1 gene showed that among patients with the resistant epilepsy and the controls, the share of people with mutant genotypes had almost identical frequencies (20%). The risk of development of resistance to AED in carriers of the genotype was statistically insignificant (N0.05). doi:10.1016/j.jns.2013.07.103 Abstract — WCN 2013 No: 1513 Topic: 1 — Epilepsy Symptomatic versus idiopathic temporal lobe epilepsies: Findings from a cohort of 75 patients Y. Hizem, A. Nasri, M. Ben Djebara, Y. Sidhom, I. Abdelkefi, A. Gargouri-Berrechid, R. Gouider. Department of Neurology/Research Unit 03/UR/08-09, Research Unit 12SP21, Razi Hospital, Tunis, Tunisia Introduction: Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Twomain varieties have been described in TLE: mesial and lateral or neocortical temporal epilepsy. Objective: To determine clinical, electrical and radiological differences between mesial and neocortical variants of temporal lobe epilepsies in idiopathic versus symptomatic groups. Methods: Retrospective study of clinical, electrical and radiological features in four groups: mesial symptomatic (MSTLE), neocortical symptomatic (NSTLE), mesial idiopathic (MITLE) and neocortical idiopathic (NITLE). Results: Total of 75 patients: 24 MSTLE, 33 NSTLE, 14 MITLE and 4 NITLE. The mean age of onset was respectively: 11.54, 22.63, 9.78 and 15.7 years. History of febrile seizures is found in 66% inMSTLE. Themain types of seizures are automatisms and visceral sensory auras in MTLE symptomatic (75% and 58% respectively) and idiopathic (43% and 71% respectively). Psychic auras are the most frequent type in NSTLE (42%) and language alterations in NITLE (100%). spike-waves are common in mesial group. Pharmaco-resistance is more frequent in MSTLE (54%) and NITLE (50%). In the symptomatic group, brain MRI shows association of other temporal lobe abnormalities to mesial sclerosis in 46%. Conclusion: Our study shows earlier age of onset with a higher frequency of febrile seizures and pharmaco-resistance in MSTLE group. The Symptomatic group of TLE is characterized by older age and higher frequency of background EEG abnormalities. Some features are shared between the symptomatic or idiopathic variants and others depend on the mesial or neocortical localization. doi:10.1016/j.jns.2013.07.104 Abstract — WCN 2013 No: 1511 Topic: 1 — Epilepsy Multimodal presurgical evaluation in children with focal cortical dysplasia WCN 2013 No: 1511 Topic: 1 — Epilepsy Multimodal presurgical evaluation in children with focal cortical dysplasia M. Sigatullina, G. Garcia, J. Muchart, M. Rebollo, J. Aparicio, F. Sanmarti. Epilepsy Unit, University Hospital Sant Joan de Deu, Barcelona, Spain Objective: To evaluate the effectiveness of multimodal presurgical evaluation in patients with focal cortical dysplasia (FCD). Methods and subjects:We performed preand postsurgical evaluation in 20 patients withmalformations of cortical development (MCD) aged from 2 months till 17 years old. All of them underwent continuous video-EEG, MRI, 18 FDG-PET and SISCOM investigations. Results: There were operated 20 patients with MCD with preand postsurgical evaluation. Themean age at neurosurgerywas 6.5 years. 18 patients had different types FCD and 2 had hemimegalencephaly. The mean period between epilepsy onset and neurosurgery was 6 years. In 15 (75%) patients the presurgical MRI (1.5 T) detected FCD correlated with focal rhythmic epileptiform discharges during video-EEG register. In 5 patients (25%) with negative MRI, 18 FDG-PET and SISCOM were useful to complete the preoperative study. Surgical procedures included 6 temporal, 10 extratemporal, 2 multilobar resections and 2 functional hemispherotomies. Brain histological analysis confirmed the diagnosis ofMCD in all cases. The outcome after 1 year of neurosurgery, according Abstracts / Journal of the Neurological Sciences 333 (2013) e1–e64 e27

Nocturnal Frontal Lobe Epilepsy Presenting as Obstructive Type Sleep Apnea

A 20-year-old man presented with sleep apnea. Polysomnography was performed and it revealed nine apneas and two hypopneas. Contrary to typical apnea, however, rhythmic epileptiform discharges appeared at bifrontal area on EEG just before the start of apnoea. Video-EEG monitoring was performed to classify these events, and to evaluate the relationship of apnoea and ictal discharge. Ictal EEG revealed paroxysmal fast activity over the bifrontal area. Ictal SPECT showed hyperperfusion in right frontal area. Given these findings, we concluded that these events were epileptic seizures presenting as obstructive sleep apnea. Antiepileptic medication was initiated, and the events were decreased. This case demonstrates that nocturnal frontal love epilepsy may be the potential cause of obstructive sleep apnea (OSA).

Subclinical seizures in children diagnosed with localization-related epilepsy: Clinical and EEG characteristics

Objective Subclinical seizures (SCSs) are characterized by paroxysmal rhythmic epileptiform discharges that evolve in time and space in the absence of objective clinical manifestation or report of a seizure. The aim of this study was to evaluate the frequency and characteristics of SCSs in children with localization-related epilepsy (LRE). Methods The results of video/EEG monitoring were reviewed to identify patients with SCS. We identified 187 children diagnosed with LRE, in 32 of whom SCSs were reported in the EEG recording. Results SCSs were reported only in the children who had received a diagnosis of either symptomatic or cryptogenic LRE. All children had a history of clinical seizure(s). The ictal onset of SCSs was most frequent from the temporal and frontal lobes. SCSs were lateralized to the left hemispheres in 19, right hemisphere in 8, and both hemispheres independently in 5 children. SCSs were more often reported in young children, and associated with a history of developmental delay, infantile spasms, and frequent seizures. EEG abnormalities included background slowing and lack of normal sleep architecture in addition to the epileptiform activity. Seizure freedom was reported less often in children with SCSs. Six patients seizure free at the time of the admission were found to have SCSs. Conclusion Subclinical seizures are not uncommon in children with LRE, in particular, with younger age, developmental disability, and medically refractory clinical course. Video/EEG monitoring will be informative in selected children with LRE to assess the seizure frequency more accurately.

Focal Electrical Status (FES): A New Finding Associated With Polymicrogyria

Polymicrogyria (PMG), a malformation of cortical organization, may, occasionally, be associated with electrical status epilepticus of sleep and focal electrical status. The aim of this study was to better characterize the latter association. This was an historic cohort study. Inclusion criteria were diagnosis of PMG on neuroimaging and presence of focal electrical status on EEG. Focal electrical status was considered when patients presented with continuous epileptiform abnormalities over a focal area on awakeness, which became bilateral and synchronous during sleep. Interictal EEGs lasted for at least 20 minutes and up to 4 hours and were performed during awakeness and sleep. Neuroimaging findings were classified as holosylvian PMG and hemispheric PMG. All patients, except one, had asymmetric neuroimaging findings, mostly on the right side. All patients had partial motor seizures, which were easily controlled with antiepileptic drugs in two of them. Despite seizure control, their EEGs still registered focal electrical status. The other four patients presented with atonic seizures and/or atypical absences. All patients showed awakeness focal electrical status that was activated by sleep. Focal electrical status is a different EEG pattern from other continuous electrographical patterns previously described, such as electrical status epilepticus of sleep, continuous epileptiform discharges, and rhythmic epileptiform discharges. Each one has its own peculiarity. Focal electrical status seems to be associated with asymmetric and extensive PMG.

Focal fast rhythmic epileptiform discharges on scalp EEG in a patient with cortical dysplasia

A distinctive scalp electroencephalographic (EEG) pattern of focal fast rhythmic epileptiform discharges (FREDs) in a 23-year-old man with symptomatic localization related epilepsy is presented. Magnetic resonance imaging (MRI) of the brain revealed cortical dysplasia over the right temporal region where the peculiar EEG abnormality was detected. We suggest that this characteristic EEG pattern may be predictive of focal cortical dysplasia (FCD). A brief review of the rhythmic EEG abnormalities in FCDs is also presented.

Physiological basis of pathophysiological brain rhythms

Focal epilepsy may be induced acutely in the brain in vivo by measures which reduce inhibition or enhance excitation. Athough the various models involve different mechanisms causing the epilepsy, their epileptiform discharge patterns vary only little. Intracellular analyses in vivo and in vitro reveal that the cellular hallmark of epileptic discharge, the paroxysmal depolarization shift, is followed by a giant hyperpolarization. The latter is comprised of several, overlapping, components with different durations, including calcium dependent potassium currents and GABA dependent inhibitions. Relative reduction of one inhibitory component is compensated by other inhibitory components. In epilepsy caused by reduction of GABAergic inhibition, the absolute duration and amplitude of GABAergic inhibition may even be increased in comparison to the responses following afferent stimulation under control conditions since the excitatory drive of the paroxysmal discharges on the interneurons is strongly increased. In some interictal discharge patterns, the enhanced inhibitions within the focus determine the refractory periods of the focus. The latter is paced by neurons from the perifocal area which show a shorter inibition associated with the interictal epileptic event. The discharge pattern of the focus may switch to other patterns, either spontaneously, or as entrained by external stimulation. Such changes are caused e.g. by progressive potassium accumulations in the extracellular space with critically small intervals of the epileptic events. It is concluded that the epileptiform discharge patterns reflect intrinsic properties of the brain, and do not very well reflect the mechanism of action of the epileptogenic model. The brain is thus equipped with inherent mechanisms which favor rhythmic epileptiform discharges under certain conditions.

Usefulness of focal rhythmic discharges on scalp EEG of patients with focal cortical dysplasia and intractable epilepsy

We examined the significance and frequency of occurrence of rhythmic epileptiform discharges (REDs) on the scalp EEGs of 74 patients with intractable partial epilepsy. We also analyzed the relationship of this abnormality to the continuous epileptiform discharges (CEDs) recorded on ECoG. Both REDs and CEDs had been found to be highly specific and sensitive indicators of focal cortical dysplastic lesions. Thirty-four patients (group I) had focal cortical dysplastic lesions (FCDLs) and 40 (group II) had non-dysplastic structural lesions. REDs were observed in 15 (44%) of the 34 patients of group I and in none of group II. REDs did not occur in isolation, were associated with more intermittent interictal spikes involving other regions, but had a greater (P < 0.05) significance for the localization of the epileptogenic area. A strong relationship was observed between the presence of REDs on scalp EEG and the occurrence of CEDs on ECoG recordings. Twelve (80%) of 15 patients with REDs had CEDs. Focal cortical dysplastic lesions are likely to be present when rhythmic epileptiform discharges are found.

Role of the hippocampal-entorhinal loop in temporal lobe epilepsy: extra- and intracellular study in the isolated guinea pig brain in vitro

This article introduces a new experimental paradigm for the study of temporal lobe epilepsy. This approach utilizes the isolated guinea pig brain in vitro preparation, which generates a pattern of hypersynchronous neuronal activity similar to the peculiar 8-30 Hz rhythm characterizing stereoelectroencephalographic hippocampal recordings in human temporal lobe epilepsy. The present report describes an attempt to identify the functional events underlying the epileptiform activities observed in this preparation. Rhythmic epileptiform discharges (EDs), here defined as population spikes (PSs) recorded from somata or dendritic layers, were induced in the hippocampal formation of the isolated guinea pig brain maintained in vitro by tetanic stimulation of the entorhinal cortex (EC). Two patterns of EDs were distinguished by performing simultaneous field potential recordings along the dentate gyrus (DG), EC, CA1, and CA3. During stage 1, the first self-sustained EDs were isolated PSs occurring at a frequency of 2-3 Hz at all levels of the entorhinal-hippocampal loop, the only exception being the DG, where no signs of synchronized neuronal discharge could be found. Over the next 30-50 sec, the temporal organization of these EDs changed dramatically. During stage 2, at all levels of the entorhinal-hippocampal loop, EDs occurred in 0.3-0.5 sec trains of 16-25 Hz population spikes interrupted by 0.7-1.3 sec silent periods. The transition between stages 1 and 2 coincided with the occurrence of population spikes in the DG. Laminar analyses and multiple simultaneous field potential recordings revealed that the trains of EDs observed in stage 2 resulted from the repetitive, sequential activation of the hippocampal-entorhinal loop. In the transverse axis, the earliest event usually occurred in the CA3 region. Thereafter, population spikes occurred sequentially in the CA1 region, EC, DG, and back to the CA3 region. Intracellular recordings confirmed that the EDs recorded extracellularly resulted from the synchronous activation of the cells in phase with the locally recorded field potentials. Dentate granule cells, layer II entorhinal cells, as well as CA1 pyramids displayed large-amplitude EPSPs crowned by an isolated action potential phase locked to the locally recorded field potential. In contrast, the activity of CA3 pyramids consisted of typical paroxysmal depolarization shifts on which bursts of action potentials of decreasing amplitude were observed. These results suggest that reentrant loop activity in the hippocampal-entorhinal circuit represents the central event in the functional organization of hippocampal epileptic discharges.