[COVID-19 with strange hallucinations and focal EEG abnormalities: Two case reports]. / Két Covid-19-beteg különös hallucinációkkal és fokális EEG-eltérésekkel.

Scientific literature about the ongoing COVID-19 disease and pandemic is considerable, though articles concentrate on the severe cases and their central nervous system manifestations. This article demonstrates two cases: middle-aged female patients who had serologically proven SARS-CoV-2 infection with mild upper airway and central nervous system symptoms. The patients reported vivid, strange, simple, and complex visual and auditory hallucinations. A characteristic element of these complex hallucinations was a talking human-shaped figure. Only three similar cases have been published; this article discusses common features of all five patients. This summary highlights that in COVID-19 cases, minor central nervous system symptoms can accompany mild or even missing upper respiratory symptoms. The cranial MRIs of the presented patients were normal, but the EEG showed focal abnormalities in localizations related to hallucinations, which emphasizes the importance of EEG in differential diagnostic procedures.

[EEG abnormalities indicating the genetic determination of epilepsies]. / Az epilepsziák genetikus etiológiájára utaló EEG-eltérések.

Genetic and acquired factors contribute to epileptogenesis in all epilepsy syndromes and patients. A comprehensive evaluation of both components of etiology is essential in every patient. In this review, the authors enumerate the EEG abnormalities indicating the genetic determination of epilepsy. The authors briefly describe generalized spike-and-wave paroxysms, focal spikes and sharp waves, photosensitivity, 4-7 Hz theta rhythm, 2-4 Hz occipital intermittent rhythmic delta activity, phi rhythm, and generalized monomorphic alpha EEG background activity. For each abnormality, the authors review prior knowledge and add recent research results. The neurophysiological meaning of the abnormalities, age distribution, the relationship to epilepsy, the role of the EEG patterns in epileptogenesis, clinical presentation, and prognosis in the individual patient are the main aspects of description and discussion. These EEG abnormalities may shape the typical, syndrome-specific phenotype, forecast severity of the disease and difficulty of treatment or pharmacoresistance, and modify the syndrome-specific general prognosis of the syndrome. Relationship to epilepsy and heritability data of the EEG abnormalities can help to estimate the risk of epilepsy in the offspring. Epilepsy syndromes are taxonomic diagnostic categories that might be enriched with neurobiological meaning and heritability relations.

[New applications of conventional EEG analysis]. / A hagyományos EEG új feladatai.

Neurophysiological research suggests that the so-called "standard" EEG analysis has been confronted with new diagnostic challenges. The findings mainly concern the occurrence, the neurophysiological and clinical significance of epileptiform EEG discharges in several neurological and psychiatric disorders. In addition to well-known interictal and ictal discharges, a growing number of recently recognized epileptiform phenomena have been described. The first reports suggested that they might be relevant for the comprehensive description of epileptic dysfunction and might contribute to diagnosis and treatment as well. However, considerable improvement of present-day "standard" EEG technique is necessary to give an appropriate answer to most challenges. Reliable registration and quantitative assessment of well-known epileptiform transients require extended electrode coverage of the head (high-density EEG) and long-term recordings including waking and sleep states to estimate frequency and dyna-mics of targeted activities. Computer-based automatic event detection is preferable to spare time and cost of the evaluation. The authors review recent progress concerning epidemiology, neurophysiology and clinical impact of well-known epileptiform transients and candidate epileptiform activities in neurological and psychiatric conditions. However, recent results need confirmation in large patient populations; therefore, research should not be restricted to a few central laboratories.

EEG-based connectivity in patients with partial seizures with and without generalization.

BACKGROUND AND PURPOSE: To investigate the neurophysiological basis of secondary generalization of partial epileptic seizures. METHODS: Inter-ictal, resting-state EEG functional connectivity (EEGfC) was evaluated and compared: patients with exclusively simple partial seizures (sp group) were compared to patients with simple partial and secondary generalized seizures (spsg group); patients with exclusively complex partial seizures (cp group) were compared to patients with cp and secondary generalized seizures (cpsg group); the collapsed sp+cp group (spcp) was compared to those who had exclusively secondary generalized seizures (sg group). EEGfC was computed from 21-channel waking EEG. 3 minutes of waking EEG background activity was analyzed by the LORETA Source Correlation (LSC) software. Current source density time series were computed for 23 pre-defined cortical regions (ROI) in each hemisphere, for the 1-25 Hz very narrow bands (1 Hz bandwidth). Thereafter Pearson correlation coefficients were calculated between all pairs of ROI time series in the same hemisphere. Z-scored correlation coefficients were compared at the group level (t-tests and correction for multiple comparisons by local false discovery rate, FDR). RESULTS: Statistically significant (corrected p<0.05) EEGfC differences emerged at specific frequencies (spsg > sg; cpsg > cp), and at many frequencies (sg > spcp). The findings indicated increased coupling between motor cortices and several non-motor areas in patients with partial and sg seizures as compared to patients with partial seizures and no sg seizures. Further findings suggested increased coupling between medial parietal-occipital areas (structural core of the cortex) and lateral hemispheric areas. CONCLUSION: Increased inter-ictal EEGfC is associated with habitual occurrence of secondary generalized seizures.

[EEG-based cerebral networks in 14 neurological disorders]. / EEG-alapú agyi hálózatok 14 neurológiai betegségben.

Background - Brain networks have not been systematically investigated yet in most neurological disorders. Purpose - To investigate EEG functional connectivity (EEGfC) networks in 14 neurological disorders. Patients - Potentially eligible patients were collected from clinical and EEG databases. All the available clinical data and EEG records were critically revised. All the patients who suffered of a single neurological disorder (out of the 14) and had a good quality EEG recording entered the study. Confoundig factors as comorbidity and CNS-active drug effects were eliminated as far as possible. EEG analysis - Three minutes of resting-state, waking EEG activity were selected for analysis. Current source density (CSD) values were computed for 2394 cortical voxels by Low Resolution Electromagnetic Tomography (LORETA). Thereafter, Pearson correlation coefficients were computed between all pairs of 23 cortical regions of interest (ROI) in each hemisphere (LORETA Source Correlation, LSC software). Computation was carried out for conventional EEG broad bands and very narrow bands (1 Hz bandwidth) between 1 and 25 Hz as well. Correlation coefficients of each group were statistically compared to our normative EEG (LSC) database by two-talied t-tests. Bonferroni-corrected p<0.05 values were accepted as statistically significant, and were graphically displayed as topographical networks. Results and conclusion - Group-specific networks were demonstrated. However, non-specific networks, charasteristic for most groups, were detected as well. Common finding were: decreased connectivity in the alpha band and increased connectivity in the delta, theta bands and upper-beta band. Decreased alpha-band connectivity presumably reflected primary lesional effects and on the other hand, non-specific vulnerability of "rich club connections". Increased connectivity in the slow bands presumably indicated adaptive-compensatory activity of brain homeostasis.

[INDIVIDUAL EVALUATION OF LORETA ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY]. / EGYEDI LORETA-ABNORMALITÁSOK VIZSGÁLATA IDIOPATHIÁS GENERALIZÁLT EPILEPSZIÁKBAN.

BACKGROUND: Contemporary neuroimaging methods disclosed structural and functional cerebral abnormalities in idiopathic generalized epilepsies (IGEs). However, individual electrical (EEG) abnormalities have not been evaluated yet in IGE patients. METHODS: IGE patients were investigated in the drug-free condition and after 3-6 month of antiepileptic treatment. To estimate the reproducibility of qEEG variables a retrospective recruited cohort of IGE patients was investigated. 19-channel resting state EEG activity was recorded. For each patient a total of 2 minutes EEG activity was analyzed by LORETA (Low Resolution Electromagnetic Tomography). Raw LORETA values were Z-transformed and projected to a MRI template. Z-values outside within the [+3Z] to [-3Z] range were labelled as statistically abnormal. RESULTS: 1. In drug-free condition, 41-50% of IGE patients showed abnormal LORETA values. 2. Abnormal LORETA findings showed great inter-individual variability. 3. Most abnormal LORETA-findings were symmetrical. 4. Most maximum Z-values were localized to frontal or temporal cortex. 5. Succesfull treatment was mostly coupled with disappearence of LORETA-abnormality, persistent seizures were accompanied by persistent LORETA abnormality. DISCUSSION: 1. LORETA abnormalities detected in the untreated condition reflect seizure-generating property of the cortex in IGE patients. 2. Maximum LORETA-Z abnormalities were topographically congruent with structural abnormalities reported by other research groups. 3. LORETA might help to investigate drug effects at the whole-brain level.

[FOCAL MOTOR SEIZURES AND STATUS EPILEPTICUS PROVOKED BY MIRTAZAPINE]. / MIRTAZAPIN ÁLTAL PROVOKÁLT FOKÁLIS MOTOROS ROHAMOK ÉS STATUS EPILEPTICUS.

The seizure-provoking effect of the tetracyclic antidepressant mirtazapine is not a well-known adverse effect of the drug. The authors report on a 39-year-old non-epileptic patient who had been treated for depression with the usual daily dose of mirtazapine. Having increased the daily dose of the drug from 30 to 45 milligrams he experienced a few clonic seizures of the right lower limb. This symptom and insomnia erroneously intended the patient to further increase the daily dose of mirtazapine, which immediately resulted in the evolution of focal clonic status epilepticus in the same limb. After admission, this condition was recorded by video-EEG and abolished by intravenous administration of levetiracetam after the intravenous clonazepam had been ineffective. Discontinuation of mirtazapine and administration of carbamazepine resulted in completely seizure-free state that persisted even after carbamazepine treatment was terminated. The clinical and laboratory data indicate the seizure-provoking effect of mirtazapine in the reported case.

Epileptic diathesis: An EEG-LORETA study.

OBJECTIVE: Epileptic diathesis is an inherited neurophysiological trait that contributes to the development of all types of epilepsy. The amount of resting-state electroencephalography (EEG) theta activity is proportional to the degree of cortical excitability and epileptic diathesis. Our aim was to explore the amount and topographic distribution of theta activity in epilepsy groups. We hypothesized that the anatomical distribution of increased theta activity is independent of the epilepsy type. METHODS: Patients with unmedicated idiopathic generalized epilepsy (IGE, n = 92) or focal epilepsy (FE, n = 149) and non-seizure patients with mild to moderate cerebral lesions (NONEP, n = 99) were compared to healthy controls (NC, n = 114). We analysed artifact-free EEG activity and defined multiple distributed sources of theta activity in the source space via low resolution electromagnetic tomography software. Age-corrected and Z-transformed theta values were compared across the groups. RESULTS: The rank of increased theta activity was IGE > FE > NONEP > NC. Both epilepsy groups showed significantly more theta activity than did the NC group. Maximum theta abnormality occurred in the medial-basal prefrontal and anterior temporal cortex in both epilepsy groups. CONCLUSIONS: We confirmed the hypothesis outlined above. SIGNIFICANCE: The common topographical pattern of increased EEG theta activity is correlated with epileptic diathesis, regardless of the epilepsy type.

Resting-state EEG theta activity reflects degree of genetic determination of the major epilepsy syndromes.

OBJECTIVE: To explore relationship between EEG theta activity and clinical data that imply the degree of genetic determination of epilepsy. METHODS: Clinical data of interest were epilepsy diagnosis and positive / negative family history of epilepsy. Study groups were: idiopathic generalized epilepsy (IGE), focal epilepsy (FE); FE of unknown etiology (FEUNK), FE of postnatal-acquired etiology (FEPA); all patients with positive / negative family history of epilepsy (FAPALL, FANALL, respectively), disregarding of the syndrome; FAP patients with 1st degree affected relative (FAP1) and those with 2nd degree epileptic relative only (FAP2). Quantitative EEG analysis assessed amount of theta (3.5-7.0 Hz) activity in 180 seconds of artifact-free waking EEG background activity for each patient and group. Group comparison was carried out by nonparametric statistics. RESULTS: Differences of theta activity were: FAPALL > FANALL (p = 0.01); FAP1 > FAP2 (p = 0.2752). IGE > FE (p = 0.02); FEUNK > FEPA (p = 0.07). CONCLUSIONS: This was the first attempt to explore and quantitatively ascertain relationship between an EEG variable and clinical data that imply greater or lesser degree of genetic determination in epilepsy. SIGNIFICANCE: Theta activity is endophenotype that bridges the gap between epilepsy susceptibility genes and clinical phenotypes. Amount of theta activity is indicative of degree of genetic determination of the epilepsies.

Inter-ictal network of focal epilepsy and effects of clinical factors on network activity.

OBJECTIVE: Aim of the study was to explore the inter-ictal, resting-state EEG network in patients with focal epilepsy (FE) and to specify clinical factors that influence network activity. METHODS: Functional EEG connectivity (EEGfC) differences were computed between 232 FE patients (FE group) and 77 healthy controls. EEGfC was computed among 23 cortical regions within each hemisphere, for 25 very narrow bands from 1 to 25 Hz. We computed independent effects for six clinical factors on EEGfC in the FE group, by ANOVA and post-hoc t-statistics, corrected for multiple comparisons by false discovery rate method. RESULTS: Robust, statistically significant EEGfC differences emerged between the FE and the healthy control groups. Etiology, seizure type, duration of the illness and antiepileptic treatment were independent factors that influenced EEGfC. Statistically significant results occurred selectively in one or a few very narrow bands and outlined networks. Most abnormal EEGfC findings occurred at frequencies that mediate integrative and motor activities. CONCLUSIONS: FE patients have abnormal resting-state EEGfC network activity. Clinical factors significantly modify EEGfC. SIGNIFICANCE: Delineation of the FE network and modifying factors can open the way for targeted investigations and introduction of EEGfC into epilepsy research and practice.

Perisylvian epileptic network revisited.

We overview here the new data about the epileptic spectrum disorders within the frame of perisylvian epileptic network since our first trial to synthetize knowledge about this system epilepsy (Halász et al., 2005). We found evidences for a continual features relating together syndromes constituting this spectrum disorder in several fields: in sharing genetic origin, in common perisylvian human communication circuitry, in NREM sleep related potentiation of interictal epileptiform discharges of the centro-temporal spike phenomenon and in the discharge related cognitive impairment, reflecting functional deficits in human communication abilities. The transformation of a part of the children to develop into a malignant course with different degree of residual cognitive loss, through compromising sleep plastic functions, by the epileptic discharges during sleep, beside pure genetic origin, is still under research. Both factual data and new conceptual approaches helps understand better the developmental childhood epilepsies.

Imaging the cortical effect of lamotrigine in patients with idiopathic generalized epilepsy: a low-resolution electromagnetic tomography (LORETA) study.

PURPOSE: Anatomical localization of the cortical effect of lamotrigine (LTG) in patients with idiopathic generalized epilepsy (IGE). METHODS: 19 patients with untreated IGE were investigated. EEG was recorded in the untreated condition and 3 months later when LTG treatment abolished the seizures. 19-channel EEG was recorded, and a total of 2min artifact-free, waking EEG was processed to low-resolution electromagnetic tomography (LORETA) analysis. Activity (that is, current source density, A/m(2)) was computed in four frequency bands (delta, theta, alpha, and beta), for 2394 voxels that represented the cortical gray matter and the hippocampi. Group differences between the untreated and treated conditions were computed for the four bands and all voxels by multiple t-tests for interdependent datasets. The results were presented in terms of anatomical distribution and statistical significance. RESULTS: p<0.01 (uncorrected) changes (decrease of activity) emerged in the theta and the alpha bands. Theta activity decreased in a large cluster of voxels including parts of the temporal, parietal, occipital cortex bilaterally, and in the transverse temporal gyri, insula, hippocampus, and uncus on the right side. Alpha activity decreased in a relatively smaller cortical area involving the right temporo-parietal junction and surrounding parts of the cortex, and part of the insula on the right side. CONCLUSIONS: LTG decreased theta activity in several cortical areas where abnormally increased theta activity had been found in a prior study in another cohort of untreated IGE patients [Clemens, B., Bessenyei, M., Piros, P., Tóth, M., Seress, L., Kondákor, I., 2007b. Characteristic distribution of interictal brain electrical activity in idiopathic generalized epilepsy. Epilepsia 48, 941-949]. These LTG-related changes might be related to the decrease of seizure propensity in IGE.

Three-dimensional localization of abnormal EEG activity in migraine: a low resolution electromagnetic tomography (LORETA) study of migraine patients in the pain-free interval.

Investigating the brain of migraine patients in the pain-free interval may shed light on the basic cerebral abnormality of migraine, in other words, the liability of the brain to generate migraine attacks from time to time. Twenty unmedicated "migraine without aura" patients and a matched group of healthy controls were investigated in this explorative study. 19-channel EEG was recorded against the linked ears reference and was on-line digitized. 60 x 2-s epochs of eyes-closed, waking-relaxed activity were subjected to spectral analysis and a source localization method, low resolution electromagnetic tomography (LORETA). Absolute power was computed for 19 electrodes and four frequency bands (delta: 1.5-3.5 Hz, theta: 4.0-7.5 Hz, alpha: 8.0-12.5 Hz, beta: 13.0-25.0 Hz). LORETA "activity" (=current source density, ampers/meters squared) was computed for 2394 voxels and the above specified frequency bands. Group comparison was carried out for the specified quantitative EEG variables. Activity in the two groups was compared on a voxel-by-voxel basis for each frequency band. Statistically significant (uncorrected P < 0.01) group differences were projected to cortical anatomy. Spectral findings: there was a tendency for more alpha power in the migraine that in the control group in all but two (F4, C3) derivations. However, statistically significant (P < 0.01, Bonferroni-corrected) spectral difference was only found in the right occipital region. The main LORETA-finding was that voxels with P < 0.01 differences were crowded in anatomically contiguous cortical areas. Increased alpha activity was found in a cortical area including part of the precuneus, and the posterior part of the middle temporal gyrus in the right hemisphere. Decreased alpha activity was found bilaterally in medial parts of the frontal cortex including the anterior cingulate and the superior and medial frontal gyri. Neither spectral analysis, nor LORETA revealed statistically significant differences in the delta, theta, and beta bands. LORETA revealed the anatomical distribution of the cortical sources (generators) of the EEG abnormalities in migraine. The findings characterize the state of the cerebral cortex in the pain-free interval and might be suitable for planning forthcoming investigations.

Valproate decreases EEG synchronization in a use-dependent manner in idiopathic generalized epilepsy.

INTRODUCTION: In order to explore the mechanism of action of valproate (VPA) in idiopathic generalized epilepsy (IGE), the effect of VPA on cortical EEG activity was investigated. HYPOTHESIS: VPA decreases EEG synchronization in the delta and theta frequency bands in a use-dependent manner in IGE patients. METHODS: First setting: EEG records of 17 untreated IGE patients (NAE group) were analyzed and compared to those of 15 healthy controls (NC group). Second setting: EEG recorded in the untreated condition (NAE) was compared to the EEG recorded in the treated condition (VPA) of the patient group. Technique and analysis: 2 min of eyes-closed, waking EEG background activity (without epileptiform potentials and artifacts) were analyzed. Absolute power (AP) and mean frequency (MF) were computed for 19 electrodes and four frequency bands (delta=1.5-3.5 Hz, theta=3.5-7.5 Hz, alpha=7.5-12.5 Hz, beta=12.5-25.0 Hz). Log-transformed data entered further analysis. Group differences were computed by means of parametric statistics including correction for multiple comparisons. The VPA-related changes (APvpa-APnae) were correlated with the degree of the baseline abnormality (APnae) and the daily dose/serum levels of VPA. MAIN RESULTS: Statistically significant (p<0.05, corrected) changes in the first setting: diffuse delta, theta, alpha AP increase, mainly right hemispheric beta AP increase was found in the NAE group, as compared to the NC group. Second setting: VPA decreased delta and theta AP. Strong correlation was demonstrated between the degree of the initial AP abnormality and the VPA-related AP decrease. AP decrease did not correlate with the daily dose and the serum level of the drug. CONCLUSION: The hypothesis that VPA decreased EEG synchronization in the delta and theta frequency bands in a use-dependent manner was supported. The findings contribute to the understanding of the action of VPA at the network level.

Decrease of global current source density predicts successful treatment in absence and juvenile myoclonic epilepsies.

OBJECTIVE: To investigate relationship between treatment efficiency and EEG background activity changes in absence epilepsy (AE) and juvenile myoclonic epilepsy (JME) patients. PATIENTS AND METHODS: EEGs of 31 patients were analysed before treatment and after six months of treatment. Three minutes of artifact-free waking EEG background activity (without epileptiform potentials) were analysed for each patient in both conditions. All the EEG samples were processed to LORETA (Low Resolution Electromagnetic Tomography). Average of all the voxel-wise current source density (CSD) values within the 0.5-8.0Hz frequency range was computed for each EEG. Fischer's exact test was used to investigate association between the global CSD changes and the therapeutic outcome. RESULTS: Tight connection was demonstrated between seizure freedom and decreased CSD, and between persisting seizures and increased CSD (p<0.001). SIGNIFICANCE: An EEG-based biomarker that predicts successful drug treatment was described.

Quantitative EEG effects of carbamazepine, oxcarbazepine, valproate, lamotrigine, and possible clinical relevance of the findings.

UNLABELLED: Quantitative EEG (QEEG) effects of therapeutic doses of carbamazepine (CBZ), oxcarbazepine (OXC), valproate (VA) and lamotrigine (LA) monotherapy were investigated in patients with beginning epilepsy. Baseline waking EEG (EEG1) was recorded in the untreated state, the second EEG (EEG2) was done after 8 weeks of reaching the therapeutic dose. Left occipital data were used for analysis. QEEG target parameters were absolute band-power (delta: AD, theta: AT, alpha: AA, beta: AB), and alpha mean frequency (AMF). Group effects (untreated versus treated condition in the CBZ, VA, OXC, LA groups) were computed for each target parameter. One group with benign rolandic epilepsy remained untreated for clinical reasons and served to estimate the QEEG test-retest differences. In addition, the individual QEEG response to each drug was calculated as (EEG2-EEG1). RESULTS: statistically significant (p<0.05) group differences indicated the QEEG domain systematically affected by the drugs. CBZ caused AT increase and AMF decrease. OXC caused AMF decrease. VA and LA did not decrease AMF (LA even increased it), but reduced broad-band power. Individual power and AMF changes showed considerable variability in each group. >0.5 Hz AMF decrease (that was reported to predict cognitive impairment in prior studies) occurred in 10/41 patients in the CBZ group but never in the OXC, VA, LA groups. The results may be utilized in planning further studies addressing the relationship between antiepileptic drugs and their CNS effects. In addition, the relationship of AED-related cognitive impairment and AMF changes was discussed.

Increased resting-state EEG functional connectivity in benign childhood epilepsy with centro-temporal spikes.

PURPOSE: To explore intrahemispheric, cortico-cortical EEG functional connectivity (EEGfC) in benign childhood epilepsy with rolandic spikes (BECTS). METHODS: 21-channel EEG was recorded in 17 non-medicated BECTS children and 19 healthy controls. 180s of spike- and artifact-free activity was selected for EEGfC analysis. Correlation of Low Resolution Electromagnetic Tomography- (LORETA-) defined current source density time series were computed between two cortical areas (region of interest, ROI). Analyses were based on broad-band EEGfC results. Groups were compared by statistical parametric network (SPN) method. Statistically significant differences between group EEGfC values were emphasized at p<0.05 corrected for multiple comparison by local false discovery rate (FDR). RESULTS: (1) Bilaterally increased beta EEGfC occurred in the BECTS group as compared to the controls. Greatest beta abnormality emerged between frontal and frontal, as well as frontal and temporal ROIs. (2) Locally increased EEGfC emerged in all frequency bands in the right parietal area. CONCLUSIONS: Areas of increased EEGfC topographically correspond to cortical areas that, based on relevant literature, are related to speech and attention deficit in BECTS children.

Forced normalisation precipitated by lamotrigine.

PURPOSE: To report two patients with lamotrigine-induced forced normalization (FN). METHODS: Evaluation of the patient files, EEG, and video-EEG records, with special reference to the parallel clinical and EEG changes before, during, and after FN. RESULTS: This is the first documented report of lamotrigine-induced FN. The two epileptic patients (one of them was a 10-year-old girl) were successfully treated with lamotrigine. Their seizures ceased and interictal epileptiform events disappeared from the EEG record. Simultaneously, the patients displayed de novo occurrence of psychopathologic manifestations and disturbed behaviour. Reduction of the daily dose of LTG led to disappearance of the psychopathological symptoms and reappearance of the spikes but not the seizures. CONCLUSIONS: Lamotrigine may precipitate FN in adults and children. Analysis of the cases showed that lamotrigine-induced FN is a dose-dependent phenomenon and can be treated by reduction of the daily dose of the drug.

Factors affecting spiking related to sleep and wake states in temporal lobe epilepsy (TLE).

The aim of the study was to investigate the influence of different clinical factors on spiking during sleep and wakefulness in temporal lobe epilepsy. The study included 38 temporal lobe epilepsy (TLE) patients who underwent long-term electroencephalography (EEG) monitoring. In addition to traditional sleep scoring, waking was subdivided into eyes opened (WEO) and eyes closed (WEC) states. The following spike measures were investigated: spiking rates for each state, mean spike rate, spiking stability across wake and sleep states and relative spike density for each state. These measures were investigated according to clinical variables, such as age, age at epilepsy onset, duration of epilepsy, seizure frequency, the presence of secondarily generalised tonic-clonic (SGTC) seizures and the data on epileptogenic lesions based on MRI. Spiking rates during most states and spiking stability showed a significant positive correlation with epilepsy duration. Relative spike density during sleep stage NREM3,4 significantly increased with age at epilepsy onset. Relative spike density during WEC was significantly higher in the presence of hippocampal sclerosis (HS). Spiking rate during REM was significantly higher if a patient had SGTC seizures. Our data provide evidence that different aspects of spiking are associated with different aspects of TLE. We suggest that spike behaviour analysis offer new aspects both for diagnosis and research.

The perisylvian epileptic network. A unifying concept.

In this work the authors provide evidences for a unifying concept of the syndromes of benign focal childhood epilepsies, Landau-Kleffner syndrome, and electrical status epilepticus in sleep treating them as a spectrum of disorders with a common transient, age dependent, non lesional, genetically based epileptogenic abnormality, the nature of which is still not known. The electro-clinical features of these syndromes are congruent with the different degree involvement of the perisylvian cognitive network and with the involvement of the thalamo-cortical associative system of variable degree. These epilepsies are characterized by the abundance of regional epileptiform discharges in sharp contrast with the rare and in several cases lacking seizures. The nature and severity of interictal cognitive symptoms are closely related to localization within the network and amount of epileptic interictal discharges. Spike-wave discharges are attributed to an alternation of overexcitation (spikes) and overinhibition (waves). The recurrent overinhibition represented by the wave of the discharges may interfere with the continuous depolarization of the cells of a large population of neurons, which is a requirement of the overt seizures. The overinhibition also interfere with cognitive processes which are correlated with the continuous presence of the fast (gamma) activity, binding the required cortical areas. Hence the recurrent inhibition works against the existence of the binding fast frequency activity. This is the assumed reason for the co-existence of the relative lack of overt seizures and in the same time for the frequently observed epileptogenic cognitive deficit symptoms ("cognitive epilepsies"). The time course of these syndromes overlaps with important developmental milestones. The frequent epileptic discharges alters the evolution of the perisylvian network developing late after early childhood and is very vulnerable for any interference in this imprinting time for speech and other cognitive functions. This spectrum of disorders represents a type of age linked, mild to severe 'epileptic encephalopathy' limited to the perisylvian network, where the cognitive impairment is caused by epileptic discharges interfering with cognitive development.