Pathological theta oscillations in idiopathic generalised epilepsy.

OBJECTIVE: To investigate spectral power, inter- and intra-hemispheric coherence in the interictal scalp electroencephalography (EEG) of 41 patients with idiopathic generalised epilepsy. METHODS: Two minutes of eyes-closed waking interictal EEG activity was analysed. Fast Fourier transformation was performed. Raw and age-regressed, Z-transformed values were computed for 19 electrodes and 4 frequency bands: absolute power (AP, ZAP), percent power (RP, ZRP), band mean frequency (MF, ZMF), inter-hemispheric (CO, ZCO) and intra-hemispheric (IC, ZIC) coherence. Compressed values (scalp averages) were computed for each parameter and 4 frequency bands. Compressed data of the patients (GE group) and the healthy controls (C group) were compared. RESULTS: ZAP across the entire 1.5-25.0 Hz range was greater in the GE than in the C group. Delta and theta ZRP was greater, alpha ZRP was less in GE than in C. ZMF and ZIC was about the same in the GE and C groups. The crucial, band-specific finding was significantly greater theta-ZCO in the GE group, in contrast to normal or decreased ZCO in the other bands. In addition, within-group correlation between ZAP of the frequency bands, correlation of ZAP and ZCO, correlation of ZIC and ZCO were different for the two groups. CONCLUSIONS: The pattern of enhanced ZAP, ZRP, ZCO, together with normal ZIC and ZMF in the theta range was a peculiar, novel finding in GE. It was incompatible with any of the known patterns of altered power and coherence due to lesional or metabolic aetiology. This pattern presumably indicates the presence of a powerful, diffuse, hypersynchronous, hypercoherent theta oscillation at the thalamo-cortical level of the brain. The role of inter-hemispheric connections in maintaining this oscillation was suggested. The other findings suggest disturbed central regulation of EEG power and coherence in the interictal state.     

Levetiracetam treatment of idiopathic generalised epilepsy

Levetiracetam (LEV) is effective for treating localisation-related epilepsy, but it is uncertain whether it is effective for treating idiopathic generalised epilepsy. We compared 12-week baseline and LEV treatment periods for patients with generalised seizure types-myoclonic, tonic-clonic and absence seizures--who had failed other anticonvulsants. The majority of 55 patients (76%) had >50% seizure reduction with LEV therapy, 40% became seizure-free; 15% discontinued LEV due to adverse events, mostly sedation. This is preliminary evidence that LEV is effective for treating idiopathic generalised epilepsy.     

Vagus nerve stimulation for refractory idiopathic generalised epilepsy.

We reviewed our experience with vagus nerve stimulation (VNS) in 165 patients with medically refractory epilepsy (138 partial epilepsy (PE), 13 symptomatic generalised epilepsy (SGE), 14 idiopathic generalised epilepsy (IGE)). Average duration of VNS therapy was 21.6 months. A 50% or greater reduction in seizure frequency was achieved in 47.1% of the PE group, 46.1% of the SGE group, and 57.1% of the IGE group. A 50% or greater reduction in seizure frequency and reduced antiepileptic drug (AED) regimen were achieved in: PE (9.4%), SGE (7.7%), and IGE (35.7%). These preliminary results suggest that VNS is an effective therapy for some patients with medically refractory IGE.     

Discontinuing antiepileptic drugs in long-standing idiopathic generalised epilepsy

Journal of Neurology - Once adults with long-standing idiopathic generalised epilepsy have achieved stable seizure remission, patients or physicians may attempt to discontinue their antiepileptic...     

EEG frequency profiles of idiopathic generalised epilepsy syndromes

The objective of this study was to investigate EEG frequency profiles (topographic distribution of spectral power data) in well-defined idiopathic generalised epilepsy (IGE) syndromes: juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), epilepsy with grand mal seizures on awakening (EGMA), and in the unified 'common IGE' (CIGE) group of these patients. Methods: Absolute and relative (percent) power values were computed from waking EEG activity by Fast Fourier Transform (FFT). Each patient group was compared to an age-matched group of healthy control persons. Results: There was a general tendency for diffuse (absolute and relative) delta-theta-alpha power excess and relative beta power deficit in all IGE groups as compared to controls. Statistically significant (P相似文献   

Electroclinical features of idiopathic generalised epilepsy with persisting absences in adult life.

OBJECTIVES: To describe the electroclinical features of typical absences persisting in adult life. METHODS: Twelve adult patients (aged 21 to 56 years) with idiopathic generalised epilepsy featuring typical absences as the prominent clinical feature were studied. All patients underwent a full clinical and neurophysiological investigation including ictal documentation of seizures. RESULTS: Neurological examination and neuroradiological investigations were normal in all cases. Clinical findings included a median age at onset of absences of 14 (range 4-32) years, almost constant tonic-clonic seizures (in 83% of patients), frequent episodes of absence status (in 33% of patients), and associated cognitive or psychiatric disturbances. Interictal EEG findings showed normal background activity, generalised paroxysms of spike waves or polyspike waves, and inconstant focal spikes (in five patients); runs of polyspikes were seen during non-REM sleep. Ictal EEG findings showed generalised spike waves at 3 Hz, sometimes preceded by multiple spikes, or more complex EEG patterns with sequences of polyspikes intermingled with spike waves or polyspike waves, showing discharge fragmentation or variation of intradischarge frequency. CONCLUSION: The results of the present study show that absences persisting in adult life may show particular clinical and EEG patterns, distinct from those in childhood or adolescence.     

Spike-wave discharge and the microstructure of sleep-wake continuum in idiopathic generalised epilepsy.

This review summarises all the evidences about the influence of different vigilance states on the occurrence of spike wave discharge (SWD) in idiopathic generalised epilepsy (IGE) patients. Numerous converging observations showed that full REM-sleep and alert wakefulness exert strong inhibition. A critical zone of vigilance which is a transitional state between waking and non-REM (NREM) sleep, and NREM sleep and REM sleep, has a promoting effect on the absence type spike wave discharge. Spike wave discharges are associated with phasic arousals without awakening and are attached to oscillation son the microstructural level of sleep, perpetuated by cyclic arousal events known as 'cyclic alternating pattern' (CAP), especially within the critical zone, but also along the whole sleep process. More specifically SWD seems to be attached to the 'A-phase' of CAP which is a reactive one and reflects synchronised NREM sleep EEG elements, like K-complexes, spindles and delta groups. The more slow wave elements are found in phase A--like in subtype A1--the more the coincidence with SWD occurs, and the more it is characterised by fast rhythms--as in subtype A2 and A3--the less the association with SWD could be observed. Since subtype A1 is associated with the first sleep cycle and with the descending branches of cycles, it is concluded that SWD appear in those dynamic moments of vigilance level oscillations which were characterised by strong sleep-like answers to arousal influences in high sleep pressure periods of sleep cyclicity. These data harmonize with another line of evidence suggesting that SWD represent the epileptic variant of the complex thalamocortical system function which is the substrate of NREM sleep EEG phenomena. In idiopathic generalised epilepsy there is a growing body of evidence that--as it was assumed by Gloor--spindles transform to SWD pattern. These data explain why those dynamic changes which evoke sleep responses are promoting for the occurrence of SWD. Adapting these data we offer a new interpretation to explain the strong activation effect of sleep deprivation in this kind of epilepsy. We assume that it is mainly due to the forced vigilance level oscillations, especially in morning, when elevated sleep pressure and circadian wake promoting forces, representing opposite tendencies, increase the amount of oscillations.     

A comparison of adult onset and "classical" idiopathic generalised epilepsy

OBJECTIVES: To report the characteristics of a population of patients with idiopathic generalised epilepsy (IGE) with age of onset over 20 years, and compare them with patients with "classical" IGE. METHODS: Data were collected from a computerised database of all patients with IGE attending a regional adult epilepsy clinic. Demographic data, epilepsy characteristics, and treatment outcomes were recorded. RESULTS: 72 patients with IGE of a total population of 844 had an age of onset over 20 years (8.5%). There was similar incidence of family history of epilepsy, EEG findings, and remission rates between those with a younger and older age of onset of IGE. There was a lower incidence of previous febrile convulsions in patients with adult onset. There were fewer patients with absence seizures in the adult onset group (15.3% v 46.4% in the "classical" group). CONCLUSIONS: IGE with onset later than the third decade was rare in the population studied. Prolonged EEG in selected patients may be helpful in diagnosing adult onset IGE, but the diagnosis of epilepsy remains clinical. Adult onset IGE shares many features with "classical" IGE, including EEG findings and prognosis, and is likely to represent a genetic epilepsy.     

Abnormal quantitative EEG scores identify patients with complicated idiopathic generalised epilepsy.

OBJECTIVE: To investigate the relationship between quantitative EEG (QEEG) scores and "complicating factors" (psychopathology, true pharmacoresistance, neurological symptoms) in idiopathic generalised epilepsy (IGE). METHODS: 35 newly referred, newly diagnosed, unmedicated IGE patients were collected in a prospective and random manner. Standard neuro-psychiatric and EEG examination was done. The patients were treated and controlled at regular visits. After 2 years of follow-up, clinical data were summarised and were compared to QEEG results. Clinical target items were neurologic and psychiatric abnormalities, proven pharmacoresistance. Patients with at least one of these items were labelled "complicated", whereas patients without these additional handicap were labelled as "uncomplicated". The 12 QEEG target variables were: Z-transformed absolute power values for three (anterior, central, posterior) brain regions and four frequency bands (1.5-3.5; 3.5-7.5; 7.5-12.5; 12.5-25.0 Hz). QEEG scores outside the +/- 2.5 Z range were accepted as abnormal. The overall QEEG result was classified as normal (0-2 abnormal scores), or pathological (3 or more abnormal scores). Clinical and QEEG results were correlated. RESULTS: All patients with psychopathology showed 4-8 positive pathological scores (power excess not confined to a single cortical region or frequency band). The two patients with pure pharmacoresistance showed pathological negative values (delta power deficit) all over the scalp. Statistically significant (P < 0.001) association was found between patients with uncomplicated IGE and normal QEEG, and between complicated IGE and pathological QEEG. Patients with neurological items had normal QEEG. CONCLUSION: Higher degree of cortical dysfunction (as assessed in the clinical setting) is reflected by higher degree of QEEG abnormalities. QEEG analysis can differentiate between IGE patients with or without psychopathology. Forecasting psychopathology may be the practical application of the findings.     

Accelerated long-term forgetting in temporal lobe but not idiopathic generalised epilepsy

Temporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF), in which memories are retained normally over short delays but are then lost at an accelerated rate over days or weeks. The causes of ALF, and whether it represents a consolidation deficit distinct from the one associated with forgetting over short delays, remain unclear. In addition, methodological issues have made results of some previous studies difficult to interpret. This study used improved methodology to investigate the role of seizure activity in ALF. Forgetting was assessed in participants with TLE (who have involvement of temporal lobe structures) and idiopathic generalised epilepsy (IGE; in which seizures occur in the absence of identified structural pathology in the temporal lobes). Learning of novel stimuli was matched between patients with TLE, patients with IGE and healthy controls matched for age and IQ. Results indicated that the TLE group showed accelerated forgetting between 30-min and three-weeks, but not between 40-s and 30-min. In contrast, rates of forgetting did not differ between patients with IGE and controls. We conclude that (1) ALF can be demonstrated in TLE in the absence of methodological confounds; (2) ALF is unlikely to be related to the experience of epilepsy that does not involve the temporal lobes; (3) neither seizures during the three-week delay nor polytherapy was associated with ALF.     

Levetiracetam in patients with generalised epilepsy and myoclonic seizures: an open label study.

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as either 'de novo' (monotherapy) or 'add-on' therapy in patients with different generalised epilepsies characterised by myoclonic seizures from an observational study. METHODS: We evaluated 35 patients (21 female, mean age 24.7 years) with different types of generalised epilepsies (juvenile myoclonic epilepsy (JME), severe myoclonic epilepsy of infancy (SMEI), Lennox-Gastaut syndrome (LGS), myoclonic-astatic epilepsy (MAE), myoclonic absences (MA), benign myoclonic epilepsy in infancy (BMEI) and 4 patients had unspecified epileptic syndromes). Patients received LEV as de novo monotherapy or add-on therapy. Seizure frequency changes and adverse events were observed. Follow-up was conducted for a period of 12 months after treatment. RESULTS: Patients received LEV 2000-3000 mg/day as de novo (n = 8) and as add-on therapy. In total, 29 (82%) of the 35 patients achieved > or = 50% seizure frequency reduction, 15 (42%) patients achieved seizure freedom while a further 14 (40%) patients achieved > or = 50-99% seizure frequency reduction. Six (17%) patients discontinued LEV due to inefficacy or seizure worsening. Not even a single patient discontinued due to adverse effects. CONCLUSIONS: Our results confirm that LEV as de novo (monotherapy) and add-on therapy at doses between 2000 and 3000 mg/day effectively reduces myoclonic seizure frequency in patients with generalised epilepsy. LEV was also well-tolerated.     

Probabilistic mapping of thalamic nuclei and thalamocortical functional connectivity in idiopathic generalised epilepsy

It is well established that abnormal thalamocortical systems play an important role in the generation and maintenance of primary generalised seizures. However, it is currently unknown which thalamic nuclei and how nuclear‐specific thalamocortical functional connectivity are differentially impacted in patients with medically refractory and non‐refractory idiopathic generalised epilepsy (IGE). In the present study, we performed structural and resting‐state functional magnetic resonance imaging (MRI) in patients with refractory and non‐refractory IGE, segmented the thalamus into constituent nuclear regions using a probabilistic MRI segmentation method and determined thalamocortical functional connectivity using seed‐to‐voxel connectivity analyses. We report significant volume reduction of the left and right anterior thalamic nuclei only in patients with refractory IGE. Compared to healthy controls, patients with refractory and non‐refractory IGE had significant alterations of functional connectivity between the centromedian nucleus and cortex, but only patients with refractory IGE had altered cortical connectivity with the ventral lateral nuclear group. Patients with refractory IGE had significantly increased functional connectivity between the left and right ventral lateral posterior nuclei and cortical regions compared to patients with non‐refractory IGE. Cortical effects were predominantly located in the frontal lobe. Atrophy of the anterior thalamic nuclei and resting‐state functional hyperconnectivity between ventral lateral nuclei and cerebral cortex may be imaging markers of pharmacoresistance in patients with IGE. These structural and functional abnormalities fit well with the known importance of thalamocortical systems in the generation and maintenance of primary generalised seizures, and the increasing recognition of the importance of limbic pathways in IGE.     

Obesity and its association with generalised epilepsy,idiopathic syndrome,and family history of epilepsy

Aim. Previous studies support the concept that obesity is a common comorbid condition in patients with epilepsy (PWE). In this study, we present the body mass index (BMI) and data from a survey to assess physical activity in a sample of PWE from an epilepsy clinic. Methods. Between June of 2011 and January of 2013, 100 PWE from an adult epilepsy clinic were included. We obtained BMI, waist circumference, and information regarding physical activity using a standardised questionnaire. Clinical, demographic, electrographic, and imaging parameters were collected from charts. Results. Mean age of patients was 40±14 (18–77) years. The BMI distribution was as follows: 2 patients (2%) underweight, 26 (26%) normal weight, 34 (34%) overweight, 25 (25%) obese, and 13 (13%) with morbid obesity. In our study, obesity was defined as having a BMI ≥30. We found 38 (38%) patients in this range. There was no difference in the rate of drug‐resistant epilepsy between obese and non‐obese patients (55 vs. 55%; p=0.05). Leisure time habit was reported in 82% of obese patients and 79% of patients without obesity. Overall, the most frequent activity was walking (70%). Factors associated with obesity were generalised epilepsy (OR: 2.7, 1.1–6.6; p=0.012), idiopathic syndrome (OR: 2.7, 1.04–7; p=0.018), and family history of epilepsy (OR: 6.1, 1.5–24.2; p=0.002). Conclusion. Our study suggests an association between obesity, idiopathic generalised epilepsy, and family history of epilepsy. Our study shows that PWE are physically active and there is no clear relation between exercise and obesity. We could not identify any association between drug‐resistant epilepsy and obesity. Absence of direct comparison with a control non‐epileptic population; a cross‐sectional design not allowing evaluation of a causal association among variables; and reliance on self‐reported physical activity are to be considered as limitations of the present study.     

No effects of the gonadal hormones on photoparoxysmal EEG responses in idiopathic generalised epilepsy

Purpose

It is accepted that the estrodiol hormone is proconvulsant and progesterone is anti-convulsant. In this study the effects of gonadal hormones on photoparoxysmal responses on EEG in idiopathic generalised epilepsy were researched.

Method

Twenty-two women with photosensitive idiopathic generalised epilepsy having regular menstrual cycles were recruited into the study. Patients presenting photoparoxysmal responses were selected from routine EEG recordings. Blood samples were taken on day 14 (E) and 25 (P) of the menstrual cycle to confirm E and P peaks. An EEG recording was performed for each patient on E and P days.

Result

No statistically significant differences were monitored with respect to frequency, duration of the photoparoxysmal responses on E and P peaks days (p > 0.05).

Comment

In this study no correlation could be demonstrated among menstrual cycle and photoparoxysmal responses.     

Levetiracetam monotherapy for primary generalised epilepsy.

PURPOSE: To evaluate the efficacy of levetiracetam in cases of refractory primary generalised epilepsy. METHODS: Three patients with refractory primary generalised epilepsy were treated with levetiracetam monotherapy; one with absence seizures, myoclonic jerks and generalised tonic-clonic (GTC) seizures one with myoclonic jerks and GTC seizures, and one with only GTC seizures. All three patients had generalised spike wave on the EEG and had failed at least three antiepileptic drugs (AEDs) before trying levetiracetam. RESULTS: All three patients tolerated levetiracetam well and became seizure free for at least 6 months. Therapeutic doses of levetiracetam ranged from 1250 to 3000 mg/day. CONCLUSION: Levetiracetam, a new AED with a novel mechanism(s) of action, should be considered for patients with refractory primary generalised epilepsy.     

Safety of newer generation anti-epileptic drugs in non-accidental overdose: an Irish population study.

Seven new anti-epileptic drugs (AEDs) have become available in Ireland over the last 10 years; data from animal models and clinical trials suggest that they have a superior safety profile to older AEDs. A specific relationship between epilepsy and psychiatric co-morbidity has long been recognised, including the relationship between epilepsy and suicide. AEDs are common agents taken in intentional drug overdoses. We undertook a study to review the frequency and outcome of non-accidental overdose with seven new AEDS in an Irish population from 1996 to 2000. METHOD: All reported cases of drug overdoses with AEDs from 1996 to 2000 were reviewed. Data was provided by the National Poisons Information Centre, Beaumont Hospital and the Central Statistics Office. Medical records from Beaumont Hospital were reviewed in specific cases of serious drug toxicities. An extensive review of published literature reviewing the safety profile of these AEDs was performed and medical literature retrieved from the databases of the pharmaceutical industry was similarly reviewed. RESULTS: Of the 164 reported cases of newer AEDs, there were no fatalities among the cases followed up. CONCLUSION: The absence of mortalities and serious consequences from deliberate self-poisoning with the newer agents is supportive evidence for the superior safety profile of the newer AEDs.     

Coexistence of focal and idiopathic generalized epilepsy in the same patient population.

PURPOSE: To review the clinical, electrographic, radiological, and pathological findings of patients with coexistent idiopathic generalized and partial epilepsy syndromes. METHODS: We performed a medical record review and a phone interview with all patients hospitalized to the Cleveland Clinic epilepsy monitoring unit (EMU) between 1992 and 2002 who fulfilled clinical and EEG criteria of coexistent partial and generalized epilepsy syndromes. RESULTS: Seven patients were identified. Two (29%) were men with a mean age of 26 years. Four had a history of febrile seizures. Family history was positive in five. Mean duration of the generalized epilepsy syndrome was 11 years, and of the focal epilepsy 18 years. An equal number of patients developed focal versus generalized epilepsy first. Interictal EEG activity was predominantly generalized. Four had video-EEG documentation of both types of seizures. In the rest, only focal seizures were recorded but interictal activity strongly suggested a coexistent generalized epilepsy. MRI showed hippocampal atrophy in all, and hippocampal dysplasia in three. Five patients had PET imaging, all with hypometabolism in areas corresponding to the ictal onset on EEG. Four patients underwent epilepsy surgery with good surgical outcome and pathological confirmation of hippocampal sclerosis in all. CONCLUSION: We found a 0.2% incidence of coexistent focal and primary generalized epilepsy. Febrile seizures and a positive family history were common. Good seizure control was achieved after temporal lobectomy, even when interictal generalized activity predominated.