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OBJECTIVE: Patients with absence epilepsy sensitivity

Highlights • We show that typical absence seizures (AS) and hyperventilation-induced high amplitude rhythmic slowing (HIHARS) or HIHARS with Altered Awareness (HIHARSAA) can coexist in the same patient, but never at the same time. • We found that alkalosis and dysfunction of the same neural network are involved in both AS and HIHARS. • AS and HIHARS should be better recognized to avoid misdiagnosis and overtreatment. • AS and HIHARS can coexist in the same patient, but never at the same time., Background Typical absence seizures (AS) are epileptic phenomena typically appearing in children 4–15 years of age and can be elicited by hyperventilation (HV). Hyperventilation-induced high-amplitude rhythmic slowing (HIHARS) represents a paraphysiological response during HV and may manifest with alteration of awareness (HIHARSAA). To date, HIHARSAA has mostly been described in patients without epilepsy. Aim To describe five patients with treatment-responsive typical AS who, after becoming seizure free, presented with HIHARSAA. Methods By using video-electroencephalographic recording (Video-EEG), we describe differential clinical characteristics and ictal electrophysiological patterns of both typical AS and HIHARSAA. Results We demonstrate that when HIHARSAA occurs in patients with typical AS there is a temporal window between the two phenomena. This suggests that the presence of typical AS precludes the appearance of HIHARSAA. Conclusions We hypothesize that alkalosis and dysfunction of the same neural network are involved in both typical AS and HIHARSAA and that their distinct electroclinic manifestations are due to the involvement of different ion channels. Significance A better understanding of the characteristics of typical AS and HIHARSAA and of the role of alkalosis in both, can help avoiding misdiagnosis and identifying more suitable therapies for typical AS.

Objective Absence status epilepticus (ASE) is a form of non-convulsive status epilepticus characterized by ongoing or intermittent epileptic activity accompanied by behavioral and cognitive changes. Herein, we assessed high-frequency oscillations in the ripple band in patients with ASE and typical absence seizures. Methods We enrolled five patients with ASE, 26 patients with childhood absence epilepsy (CAE), and 15 patients with juvenile absence epilepsy (JAE). We performed time–frequency analysis of electroencephalogram data for ictal absence seizures at each electrode to assess the high frequency activity (HFA) rate, peak frequency, and peak power. Results The average HFA rates were 60.7%, 20.8%, and 12.9% in ASE, CAE, and JAE patients, respectively. The average peak frequencies were 126.4 Hz, 120.9 Hz, and 126.1 Hz in ASE, CAE, and JAE patients, respectively. The average peak power values were 2,388.8 μV2, 120.9 μV2, and 126.1 μV2 in ASE, CAE, and JAE patients, respectively, and all epilepsy groups exhibited frontal-dominant ripple distribution. Conclusion ASE patients presented higher power and frontal dominant ripples of absence seizure, compared to CAE and JAE patients. Significance Future studies should utilize scalp-recorded ripples as a biomarker of absence epilepsy. This may aid in the development of novel treatment strategies for ASE.

OBJECTIVE: To characterize in detail the electroclinical features of typical absence seizures and elucidate whether EEG or semiology features, alone or in combination, can predict long-term therapeutic outcome. METHODS: We analysed video-EEG recordings from 213 typical absence seizures from 61 patients with idiopathic generalized epilepsy. We extracted semiological features, in addition to hallmark manifestations (motor/behavioural arrest, non-responsiveness), their location, timing and frequency. We evaluated the duration and frequency of generalized spike-wave discharges and the presence of polyspikes. We used a supervised machine-learning approach (random forest) to search for classifier features for long-term therapeutic outcome (>one year). RESULTS: Besides the hallmark manifestations, additional semiological features were identified in 87% of patients (75% of seizures). The most common additional semiological features were automatisms and eye blinking (observed in 45% and 41.5% of seizures, respectively). Automatisms were associated with longer seizure duration, and oral automatisms occurred earlier compared to limb automatisms (4.03 vs. 6.19 seconds; p=0.005). The mean duration of the ictal spike-wave discharges was nine seconds, and the median frequency was 3 Hz. Polyspikes occurred in 46 seizures (21.6%), in 19 patients (31%). Median follow-up was five years, and 73% of the patients were seizure-free at the end of the follow-up. None of the semiological features, alone or in combination, were predictors of therapeutic outcome. The only significant classifier was the presence of polyspikes, predicting a non-seizure-free outcome with an accuracy of 73% (95% CI: 70-77%), positive predictive value of 92% (95% CI: 84-98%) and negative predictive value of 60% (95% CI: 39-81%). SIGNIFICANCE: Semiological features, in addition to behavioural arrest and non-responsiveness, are common in typical absence seizures, but they do not predict long-term therapeutic outcome. The presence of polyspikes has a high positive predictive value for unfavourable therapeutic outcome, and their presence should therefore be included when reporting EEGs in patients with typical absence seizures.

Background Sunflower syndrome (SFS) is a rare childhood-onset generalized epilepsy characterized by photosensitivity, heliotropism, and drug-resistant stereotyped seizures maybe self-induced by hand-waving maneuvers. Data on the long-term prognosis are scantly and evidence over best treatment strategies is lacking. Methods We retrospectively describe the electroclinical features, and therapeutic response in a group of 21 patients with SFS, without intellectual disability. Results 16 patients were female (67%), with a median age at onset of 7 years. In all patients, ictal episodes began with sun-staring, and hand-waving in front of the sunlight, accompanied by brief typical absence seizures. 17 patients (81%) showed interictal EEG abnormalities, mainly characterized by spike and polyspike-and-wave discharges. Ictal epileptiform activity occurred approximately less than one second after the start of hand-waving. At the last follow-up (median length 8.2 years), 12 patients (57%) were drug-resistant. Nine of them (75%) achieved seizure control with the use of tainted lenses, either alone or compared with anti-seizure medications (ASM). Disappearance of seizures was associated with EEG improvement/normalization when tinted glasses were used during EEG recordings. Conclusion While the clinical and EEG characteristics of SFS are well defined, the best therapeutic approaches are still under debate. Our data confirms a high rate of drug-resistance and frequent need of polytherapy. Of note, in drug-resistant patients, lenses (but not ASM) were able to suppress PPR in our patients while wearing lenses. Regarding the role of lenses, we do not only rely on the PPR reduction but also clinically by the reduction of seizures. Although additional data are needed, lenses seem to have a powerful potential role for the management of SFS.

Childhood absence epilepsy (CAE) is the most common pediatric epilepsy syndrome and is characterized by typical absence seizures (AS). AS are non-convulsive epileptic seizures characterized by a sudden loss of awareness and bilaterally generalized synchronous 2.5–4 Hz spike and slow-wave discharges (SWD). Gamma butyrolactone (GBL) is an acute pharmacological model of AS and induces bilaterally synchronous SWDs and behavioral arrest. Despite the long use of this model, little is known about its strain and sex-dependent features. We compared the dose-response profile of GBL-evoked SWDs in three rat strains (Long Evans, Sprague-Dawley, and Wistar), and examined the modulatory effects of estrous cycle on SWDs in female Wistar rats. We evaluated the number of seizures, the cumulative time seizing, and the average seizure duration as a function of dose, strain, and sex/estrous phase. Long Evans rats displayed the greatest sensitivity to GBL, followed by Wistar rats, and then by Sprague-Dawley rats. GBL-evoked SWDs were modulated by estrous cycle in female rats, with the lowest sensitivity to GBL occurring during metestrus. Wistar rats showed the greatest variability as a function of dose, and the least variability within dose; these features make this strain desirable for interventional studies. Moreover, our finding that the SWD response to GBL differs as a function of estrous cycle underscores the importance of cycle monitoring in studies examining female animals using this model. Together, these strain and sex-dependent findings provide guidance for future studies.

Typical absence seizures are observed in various epilepsy syndromes, however, few series have focused on early-onset absence epilepsy (EOAE). We aimed to evaluate the occurrence of this seizure type in children under 4 years of age in order to evaluate their electroclinical characteristics and outcome. We retrospectively studied (2006-2014) the electroclinical features of children with normal development and typical absence seizures starting before the age of 4 (with available pre-treatment video-EEG). Nine patients were included. Among them, eight patients had rhythmic myoclonic jerks involving the muscles of the upper face (eyebrows and eyelids) or neck, present from the onset to the end of the typical absence discharge. The myoclonia were synchronous with spike-wave complexes. One patient with GLUT-1 deficiency was refractory to antiepileptic polytherapy. The other eight became seizure-free; five with one antiepileptic drug and three with a combination of two drugs. The treatment was successfully withdrawn in five of the six patients who achieved two years of seizure freedom. None of them exhibited any other seizure type. Four of the eight patients with normal schooling required some support. We observed a positive correlation between the duration of absence seizure and the age of the patient at examination. Most of the patients under four years with only typical absence seizures had EOAE, and the motor symptoms may represent a distinctive age-related feature of EOAE. Further investigations are required to better correlate the role of brain maturation with the duration of the absence. [Published with video sequence on www.epilepticdisorders.com].

In this article, we have traced back the history of typical absence seizures, from their initial clinical description to the more recent nosological position. The first description of absence seizures was made by Poupart in 1705 and Tissot in 1770. In 1824, Calmeil introduced the term "absences", and in 1838, Esquirol for the first time used the term petit mal. Reynolds instead used the term "epilepsia mitior" (milder epilepsy) and provided a comprehensive description of absence seizures (1861). In 1854, Delasiauve ranked absences as the seizure type with lower severity and introduced the concept of idiopathic epilepsy. Otto Binswanger (1899) discussed the role of cortex in the pathophysiology of "abortive seizures", whereas William Gowers (1901) emphasized the importance of a detailed clinical history to identify nonmotor seizures or very mild motor phenomena which otherwise may go unnoticed or considered not epileptic. At the beginning of the 20th Century, the term pyknolepsy was introduced, but initially was not universally considered as a type of epilepsy; it was definitely recognized as an epileptic entity only in 1945, based on electroencephalogram (EEG) recordings. Hans Berger, the inventor of the EEG, made also the first EEG recording of an atypical absence (his results were published only in 1933), whereas the characteristic EEG pattern was reported by neurophysiologists of the Harvard Medical School in 1935. The discovery of EEG made it also possible to differentiate absence seizures from so called "psychomotor" seizures occurring in temporal lobe epilepsy. Penfield and Jasper (1938) considered absences as expression of "centrencephalic epilepsy". Typical absences seizures are now classified by the International League Against Epilepsy among generalized nonmotor (absence) seizures.

Purpose To investigate the efficacy and safety of long-term lamotrigine (LTG) monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures. Methods Six Japanese patients and one South Korean patient were enrolled in the extension phase of the study after completing the 12-week maintenance phase of an open-label clinical study of LTG monotherapy. During the extension phase, patients underwent efficacy and safety evaluation every 12 weeks. Results Of the seven patients, six patients completed the extension phase. The seizure-free rate confirmed by hyperventilation (HV)-electroencephalography ranged from 71.4% to 100.0% at each visit up to Week 168 of the extension phase. Similar effects were confirmed by HV-clinical signs and seizure diaries. Although no unexpected adverse events were observed, one Japanese patient was withdrawn from the extension phase due to mild drug-related rash developed 842 days after the start of LTG. Conclusion Although the number of patients is limited, long-term LTG monotherapy appeared to be effective and generally well tolerated in Japanese and South Korean pediatric patients with typical absence seizures.

Absence seizures are associated with generalized 2.5–5 Hz spike-wave discharges in the electroencephalogram (EEG). Rarely are patients, parents, or physicians aware of the duration or incidence of seizures. Six patients were monitored with a portable EEG-device over four times 24 h to evaluate how easily outpatients are monitored and how well an automatic seizure detection algorithm can identify the absences. Based on patient-specific modeling, we achieved a sensitivity of 98.4% with only 0.23 false detections per hour. This yields a clinically satisfying performance with a positive predictive value of 87.1%. Portable EEG-recorders identifying paroxystic events in epilepsy outpatients are a promising tool for patients and physicians dealing with absence epilepsy. Albeit the small size of the EEG-device, some children still complained about the obtrusive nature of the device. We aim at developing less obtrusive though still very efficient devices, e.g., hidden in the ear canal or below the skin., Ambulatory EEG setup for very long-term recordings on children with absence seizures.

Purpose Generalized paroxysmal fast activity (GPFA), an EEG pattern with variable frequency and duration, is usually noted in symptomatic/cryptogenic generalized epilepsies. However, GPFA has also been reported in a few patients with genetic generalized epilepsy (GGE) who presented with typical absence seizures (TAS). Our aim was to report the results of long-term follow-up and genetic findings in these patients. Methods We investigated all EEGs of adult GGE patients with TAS, and identified 12 patients with GPFA (8.3% of adult GGE patients with TAS). Ten of these patients were available for long-term follow up. Their clinical and electroencephalographic courses and genetic features were investigated. The control group was composed of 24 adult GGE patients who also had TAS, but lacking GPFA with a similar follow-up duration in the same epilepsy center. Results The mean age at GPFA detection was 33±16.6 (16–71 years) and 80% still had GPFA in their last EEG. The duration of epilepsy and persistence of TAS were both significantly longer in the GPFA group despite a similar follow-up duration. Sixty percent of the GPFA group had consanguineous parents, whereas this rate was only 4.17% in the control group. Seven relatives of the GPFA group also had epilepsy. We could not show any known mutations in two families. At the end of the follow-up, none of the patients with GPFA was dependent in self-care, despite continuing seizures. Conclusion Our study shows that GPFA is an ignored EEG pattern of adult GGE patients with TAS, indicating a long and non-remitting course in almost all of the patients.

Generalised-onset absence seizures can be resistant to treatment with currently available antiepileptic drugs. Ezogabine (retigabine), a potassium channel opener, is approved for the treatment of focal-onset seizures. This is a case report of an adult with childhood absence epilepsy whose daily absence seizures ceased with adjunctive ezogabine. A 59-year-old woman, with a history of typical absence seizures since the age of 6 years, had multiple seizures daily despite trials of over 11 antiepileptic drugs. While taking lamotrigine and zonisamide, ezogabine at 50 mg daily was added. The dose was slowly increased and once a total dose of only 200 mg/day was reached, she became seizure-free for three months. After subsequently discontinuing zonisamide, absence seizures returned. Further increasing the ezogabine to 400 mg/day, in addition to lamotrigine, did not restore seizure freedom, but adding back zonisamide at half dose again reduced their frequency. Ezogabine at low dose, added to lamotrigine and zonisamide, led to sustained absence seizure freedom. The return of seizures after zonisamide discontinuation suggests that the seizure freedom may have been the result of the different mechanisms of action of the antiepileptic drugs.

Epilepsy is a disorder of neural networks that is characterized by spontaneous recurrent seizures. The role of GABAB receptor-mediated mechanisms in the pathogenesis of seizures depends upon neural networks involved, which determine the seizure type. Generalized seizures involve diffuse, bi-hemispheric neuronal networks, while focal seizures involve regional brain networks. GABAB receptor agonists have been shown to diminish seizure activity in mouse models of both generalized convulsive and focal seizures. However, generalized non-convulsive seizures such as typical and atypical absence seizures (AASs) characteristically are exacerbated by GABAB receptor agonists and blocked by GABAB receptor antagonists. The reason for this dichotomy is the involvement of thalamic circuitry in both typical and atypical absence seizures. Thalamocortical circuitry underpins typical absence seizures (TASs) and hippocampal-thalamocortical circuitry is involved in AASs. In addition, high doses of GABAB receptor agonists active at the GABAB receptor/G-protein coupled inwardly rectifying potassium 2 (GIRK2) channel recently have been shown to induce the phenotype of a specific catastrophic epilepsy syndrome of childhood, infantile spasms, in mice. Therefore, GABAB receptor-mediated mechanisms can be pro- or anti-convulsant depending on the nature of the pathological neuronal networks involved. Although there are pre-clinical data in support of the efficacy of GABAB receptor agonists and antagonists in specific experimental models of seizures, these data have not been translated into the clinical arena because of the potential for downstream adverse effects. The therapeutic goal for the use of these compounds in epilepsy awaits a strategy that targets only those GABAB receptor for specific networks that are involved in a given pathological state.

SUMMARY The therapeutic effects of sodium valproate and ethosuximide were compared in a prospective, randomised study of 28 children whose absense attacks were associated with 3-per-second spike and wave activity in the EEG. The two drugs were equally effective in the control of absence attacks. When patients failed to respond to the initial drug prescribed, a response occurred with the alternative drug in all but one child. Complete or partial remission with sodium valproate was associated with serum levels ranging from 312 to 849mol/1 and to ethosuximide with levels from 106 to 614mol/l. Acute pancreatitis occurred in one patient on sodium valproate, whose serum levels exceeded 800mol/l. RESUME Etude comparative entre l'ethosuximide et le valproate de sodium dans le traitement des absences petit mal typiques L'action therapeutique du valproate de sodium et de l'ethosuximide a ete comparee au cours d'une etude prospective randomisee de 28 enfants dont les absences critiques etaient associees a des pointes-ondes de frequence 3 par seconde a l'EEG. Les deux medications se sont revelees d'action egale dans le controle des absences. Une reponse positive avec la seconde medication est survenue chez tous les enfants sauf un lorsque la premiere medication prescrite etait inefficace. Les reponses excellentes ou bonnes au valproate de sodium etaient associees avec des taux seriques allant de 312 a 849mol/litre, pour l'ethosuximide avec des taux de 106 a 614mol/litre. Une pancreatite aigue est survenue chez un malade traite au valproate de sodium dont les taux seriques depassaient 800mol/litre. ZUSAMMENFASSUNG Eine vergleichende Studie von Ethosuximid und Sodium Valproat bei der Behandlung typischer Absencen (Petit Mal) Die therapeutische Wirkung von Sodium Valproat und Ethosuximid wurde in einer prospektiven randomisierten Studie bei 28 Kindern verglichen, deren Absencen mit 3/sec Spike-Wave Aktivitat im EEG einhergingen. Beide Medikamente waren bei der Behandlung der Absencen gleich wirksam. Wenn Patienten auf das zuerst verschriebene Medikament nicht ansprachen, dann wurde bis auf eine Ausnahme bei allen ein Erfolg mit dem anderen Medikament erzielt. Ein hervorragender bis guter Erfolg wurde beim Sodium Valproat mit Spiegeln von 312–849mol/l und beim Ethosuximid von 106–614mol/l erreicht. Bei einem Patienten trat unter Sodium Valproat mit einem Spiegel uber 800mol/l eine akute Pankreatitis auf. RESUMEN Estudio comparativo entre la etosuccimida y el valproato sodico en el tratamiento de las crisis de ausencia tipicas (pequeno mal) Los efectos terapeuticos del valproato sodico y la etosuccimida fueron comparados en un estudio prospectivo al azar en 28 ninos cuyas crisis de ausencia iban asociadas con una actividad en el EEG de punta-onda de 3 por segundo. Ambas medicaciones eran igualmente efectivas en el control de las crisis de ausencia. Cuando los pacientes no respondian a la medicacion inicial, se obtenia respuesta con el otro farmaco en todos los casos excepto uno. Una respuesta excelente o buena al valproato sodico iba asociada a niveles de valproato de 312 a 849mol/l, y a niveles de etosuccimida de 106 a 641mol/l. En un paciente aparecio una pancreatitis tomando valproato y con niveles en sangre que sobre pasaban los 800mol/l.

Recent interest in the anticonvulsant effects of acetone has stemmed from studies related to the ketogenic diet (KD). The KD, a high-fat diet used to treat drug-resistant seizures, raises blood and brain levels of three ketones: beta-hydroxybutyrate, acetoacetate, and acetone. An obvious question is whether these ketones have anticonvulsant properties. We found that neither beta-hydroxybutyrate nor acetoacetate has proven to be anticonvulsant. Acetone, however, is clearly anticonvulsant at physiological, and near-physiological, nontoxic concentrations. Despite knowledge of acetone's anticonvulsant properties since the 1930's, acetone had never been characterized using the standard animal seizure tests. In our recent experiments, acetone was found to be active in animal models of tonic-clonic seizures, typical absence seizures, complex partial seizures, and atypical absence seizures associated with Lennox-Gastaut syndrome. Therapeutic indices are either comparable or better than that of valproate, a standard broad-spectrum anticonvulsant. A number of acetone-like molecules have also been tested, and these also show good potency up to a "cutoff" point of nine carbons contained in the side chain. Above this number, potency disappears, suggesting the possibility of a receptor for acetone and its analogs.

We applied linear and nonlinear synchronization measures to characterize the synchrony between cortical regions and detect cerebral epileptic states in scalp EEG recordings recorded prior and during typical absence seizures. An overall rapid increase in the synchronization level between different cerebral regions was observed during the ictal state. During the interictal state, the degree of interdependence between EEG channels was significantly less than that observed in the ictal state (p

Both genetic and acquired factors play important roles in the development of childhood absence epilepsy. This article describes a girl with mental retardation, probably due to a perinatal complication, who had typical absence seizures with characteristic electroencephalographic findings of childhood absence epilepsy, including normal background activity. This patient was subsequently found to have a strong genetic predisposition, which was suggested by the fact that childhood absence epilepsy also developed in her younger brother. Except for the mental subnormality, the electroclinical features of this patient satisfied the diagnostic criteria for childhood absence epilepsy. This case raises the question about diagnostic consideration of childhood absence epilepsy in association with cerebral pathology for genetically predisposed individuals.

Summary Purpose: To evaluate the role of ethosuximide, sodium valproate and lamotrigine in children and adolescents with typical absence seizures (AS). Methods: A systematic review of randomized controlled trials that included children or adolescents with typical absence seizures who received treatment with ethosuximide, sodium valproate or lamotrigine. Results: Four RCTs fulfilled the inclusion criteria. Due to the heterogeneity of the studies the results could not be pooled in a meta-analysis. Conclusions: We found no reliable evidence to inform clinical practice. The design of further trials should be pragmatic and compare one drug with another.

Near-infrared spectroscopy (NIRS) is a noninvasive method that allows the assessment of activation-induced cortical oxygenation changes in humans. It has been demonstrated that an increase in oxygenated and a decrease in deoxygenated haemoglobin can be expected over an area activated by functional stimulation. Likewise, an inverse oxygenation pattern has been shown to be associated with cortical deactivation. The aim of the current study was to determine the oxygenation changes that occur during absence seizures. We performed ictal NIRS simultaneously with video-EEG telemetry in three adult patients with typical absence seizures. NIRS probes were placed over the frontal cortex below the F1/F2 leads. During all absence seizures studied, pronounced changes in cerebral Hb-oxygenation were noted and there were no changes in the interval. We observed a reproducible decrease in [oxy-Hb] and an increase in [deoxy-Hb] during absence seizures indicating a reduction of cortical activity. Oxygenation changes started several seconds after the EEG-defined absence onset and outlasted the clinically defined event by 20-30 s.

We studied the occurrence of epileptic seizures in 72 children from war-affected and 39 children from non-war-affected areas during and after the 1991-1992 war in Croatia. During the war, children from war-affected areas who had "stable" epilepsy before the war and regularly took antiepilepsy medications had epileptic seizures more often than children from areas not affected by the war. In 2002, all children (n=10) whose first epileptic seizure was related to a stressful event had a "stable" condition, whereas 4 of 10 children whose first epileptic seizure was not stress-related had an "unstable" condition. Typical absence seizures were observed in 6 of 10 children in the stress-related group and none in the non-stress-related patient group. Stressful life events can be provocative factors for the occurrence of epileptic seizures. Typical absence seizures are more likely to be provoked by stress then other types of epileptic seizures.

Introduction - Lamotrigine is licenced in many countries for use in patients with partial seizures. Evidence suggests that it may also be effective in generalised epilepsies. Material & methods - We analysed retrospectively our patients with idiopathic generalised epilepsy with refractory absences. Results - Fifteen patients with idiopathic generalised epilepsies were identified who had been treated with lamotrigine for 3 months or more. All patients were also treated with sodium valproate. Fourteen patients had active absences. Nine (64%) had a total or virtual cessation of absences and in a further patient they became milder and less frequent. One patient reported an increase in seizures. The effective dose of lamotrigine was 1.6-3.0 mg/kg/day in children and 25-50 mg/day in adults. Patients who responded did so after the first or second dose. Lamotrigine was well tolerated. Conclusion - Low-dose lamotrigine added to sodium valproate appears to be effective in typical absence seizures. A therapeutic interaction of the two drugs seems likely.

Ein 67⁄12-jähriger Knabe präsentierte sich mit Allgemeinzustandsverschlechterung, Kopfschmerzen und nuchaler Lymphadenopathie seit mehreren Wochen zur weiteren Abklärung. Zusätzlich bestanden Episoden mit typischen Absenzen. Serologisch und mittels Liquoruntersuchung konnte eine Neuroborreliose nachgewiesen werden. Gleichzeitig zeigte der EEG-Befund eine typische Absenzen-Epilepsie. Nach Therapie mit Ceftriaxon i.v. für 14 Tage und Beginn einer antiepileptischen Therapie mit Ethosuximid trat eine schnelle Besserung des Zustandes ein. Die Absenzen-Epilepsie ist niemals vorher in der Literatur als Folge einer Neuroborreliose beschrieben worden. Wir gehen von einer Koinzidenz der beiden Entitäten aus.

All doctors caring for children with paroxysmal disorders know that an important differential diagnosis for absence seizures (both typical in the ‘normal’ child and atypical in the child with neurodevelopmental problems) and to a lesser extent complex focal seizures is daydreaming and childhood preoccupation. Indeed when, in preparation for writing this report, I audited over a four month period those children referred for ‘blank episodes’ and similar concerns to my rapid access epilepsy clinic where I see patients with suspected new-onset seizures, I made a diagnosis of epilepsy in 5 cases and of probable day dreaming / childhood preoccupation in another 5. However, with the exception of brief references to daydreaming/preoccupation in textbooks, usually in the context of considering the differential diagnosis of typical absence seizures, there is virtually nothing published on this subject. A Medline search of ‘day dreams’, ‘day dreaming’ and ‘preoccupation’ yields very few hits and none are relevant to the consideration of the differential diagnosis of paroxysmal events in children. What follows, therefore, is personal opinion, albeit from a clinician who has a special interest in absence seizures in children.

Single photon emission computed tomography (SPECT) is known to reveal localized hyperperfusion during partial seizures, but is rarely performed in idiopathic generalized epilepsies. We report the ictal SPECT findings in a typical absence seizure. This 35-year-old woman with childhood absence epilepsy underwent prolonged electroencephalogram (EEG)-video monitoring, during which many stereotyped typical absence seizures were recorded. These consisted of brief staring spells with arrest of activity, associated with generalized 3 Hz spike-wave complexes on EEG. Following intravenous (i.v.) injection of 17.6 millicuries of Tc-99m Bicisate, SPECT was performed. The injection was performed during hyperventilation that induced a typical absence. Compared to the baseline SPECT scan that was normal, the ictal scan showed a generalized reduction in cortical activity. These findings do not support the "cortical" theory of typical absence seizures and the genesis of the 3 Hz spike-wave complexes. They may indeed support the subcortical or "centrencephalic" hypothesis.

Of 1300 epileptic patients 76 (5.8%) were found to have juvenile myoclonic epilepsy (JME). These 76 patients were examined at the epilepsy outpatient clinic of Bakirkoy State Hospital for Neurological and Psychiatric Diseases between 1991 and 1996 and data obtained were analysed retrospectively. Clinically typical absence seizures were reported in 40.8%, myoclonic jerks in 100%, and generalized tonic-clonic seizures in 82.9% of the patients. Neurological and mental examination was normal for all patients with the exception of three cases; two with essential tremor and one with minimal dysarthria. Precipitating factors were noted in 85.5% of cases. Abnormal EEG was recorded in 73 (6.1%) patients. Abnormalities mainly consisted of generalized discharges of spike/polyspike and slow-wave (86.6%) and generalized paroxysmal theta or delta (9.2%). Fifteen (19.7%) had focal abnormalities and 20 (26.4%) had photoconvulsive discharges. Of the 76 patients, 40 (52.6%) were not diagnosed at the initial interview; definite diagnosis was delayed by a mean of 5.9 years. As a result of misdiagnosis at the initial interview 40 patients had been administered AED except for valproate. After reassessment of clinical and EEG findings, the medication was changed to valproate therapy. As a result, 65 of our WE patients (85.5%) were seizure free after a one-year follow-up period.

Epilepsy, a common childhood condition, is largely managed by general paediatricians. To assess whether recent management guidelines are being met, we undertook a prospective questionnaire-based survey of children with epilepsy, attending the general paediatric out-patient clinic, at the Royal Liverpool Children's Hospital, Alder Hey. Ninety-one children were identified over seven months—giving a prevalence of epilepsy in this out-patient population of 13.7/1000. Fifty-four per cent were diagnosed as having tonic-clonic, 16% partial and 5% typical absence seizures. Forty-two per cent received carbamazepine and 33% sodium valproate, as monotherapy, and 7% were treated with multiple antiepileptic drugs (AEDs). Correlation between AED and seizure type was often inappropriate as was the routine measurement of blood level of AEDs. Correlation between seizure frequency and clinic visits was generally acceptable with those children experiencing frequent seizures attending most often. Specialist paediatric neurologist advice was sought in only 14% of children; 19 of the 28 children with the most poorly controlled seizures were not referred for a specialist opinion. This study has demonstrated a poor understanding of seizure/syndrome classification: the frequent inappropriate use of AEDs and their blood level measurement and inadequate referral for specialist advice. Recognized guidelines are not being followed, nor are standards being met by many general paediatricians. There is a clear indication for more extensive education and the need to provide clear recommendations for the management of epilepsy in children.

We describe a method for the characterization of electroencephalographic (EEG) signals based on a model which features nonlinear feedback. The characteristic EEG 'fingerprints' obtained through this approach display the time-course of nonlinear interactions, rather than aspects susceptible to standard spectral analysis. Fingerprints of seizure discharges in six patients (five with typical absence seizures, one with complex partial seizures) revealed significant nonlinear interactions. The timing and pattern of these interactions correlated closely with the seizure type. Nonlinear autoregressive (NLAR) analysis is compared with other nonlinear dynamical measures that have been applied to the EEG.

The characterization of a seizure as generalized or focal onset depends on a basic knowledge of the underlying pathophysiology. Recently, an uncommon phenomenon in generalized epilepsy—evolution of seizures from generalized to focal followed by secondary generalization—was reported for the first time. We describe a 15-year-old boy, initially classified as having partial epilepsy, who had a typical absence seizure that became focal with second secondary generalization (double generalization). On the basis of these findings his epilepsy was classified as juvenile absence epilepsy and his treatment was changed, resulting in seizure freedom. This is the first report of this unusual electroclinical evolution in a patient with juvenile absence epilepsy. The recognition of this particular pattern allows correct classification and impacts both treatment and prognosis.

The clinical symptoms and electroencephalographic (EEG) features of typical absence seizures, including transverse topographical analysis (TTA), were studied retrospectively using a simultaneous EEG-VTR system in 36 children aged between 3 and 17 years. Complex absences were more common than simple, and oral automatisms were the most frequent complex symptoms. Occurrence of complex symptoms was directly proportional to the length of seizures. There was no association between lateral TTA type and simple absences. Prognosis was favorable in patients with long seizure duration ( P ), bilaterally synchronous monomorphic spike-waves throughout the seizure discharges (BSMTSD) ( P ) and lateral TTA type ( P ). Two different mechanisms of origin for BSMTSD/non-BSMTSD and lateral/non-lateral TTA types are probably responsible for the difference in prognosis. Favorable prognosis in patients with long seizures is discussed in relation to the duration of the illness. EEGs with BSMTSD and lateral TTA type may indicate a favorable prognosis in children with absence seizures.

Eighteen women and five men had typical absences. These included 10% of a consecutive hospital series of 200 adult patients with epileptic disorders. The absences began between the ages of seven and 46 years and varied in type and severity. Twenty patients also had generalised tonic-clonic seizures, ranging in frequency from one in a lifetime to one per month. Myoclonic jerks of the limbs occurred in 11 patients but were not associated with the absence attacks. Eyelid myoclonus consistently occurred with absence attacks in four patients and perioral myoclonus in two patients. Absence status occurred in five patients. Absence seizures were frequently unrecognised or misdiagnosed as complex partial seizures. Satisfactory control was achieved with sodium valproate. Electroencephalography, particularly video-electroencephalography, was invaluable in the diagnosis, but focal abnormalities in seven patients might have been erroneously interpreted as indicating partial seizures. This series showed that clinical and EEG manifestations are often syndrome-related and that there are more epileptic syndromes with typical absences than those presently recognised.

Objective: To analyze the electroclinical features of children with childhood absence epilepsy (CAE) and discuss the diagnostic criteria for CAE. Methods: The video-electroencephalogram (VEEG) database in our hospital was searched using “absence seizures” and “3-Hz generalized spike and waves (GSW)” as key-words. Other epileptic syndromes with typical absence seizures were carefully excluded. Children meeting the CAE diagnostic criteria of the International League Against Epilepsy (ILAE) in 1989 were further evaluated with the diagnostic criteria proposed by Panayiotopoulos in 2005. Results: Totally 37 children met the 1989 ILAE criteria of CAE. The onset age of absence seizures ranged from 3 to 11 years. All patients had frequent absence seizures (5–60 times per day). Two patients (5.4%) had generalized tonic-clonic seizures. Hyperventilation induced absences in all patients. VEEG confirmed that 7 patients (18.9%) had only simple absences, 25 patients (67.6%) had only complex absences, and 5 patients (13.5%) had both simple and complex absences. Ictal EEG showed 3 Hz GSW discharges in all patients. The seizure duration ranged from 3 to 40 s. Four patients (10.8%) had two spikes per wave in ictal EEG. GSW fragments were found in 29 patients (78.4%) during sleep. Interictal polyspikes and waves were present in 17 patients (45.9%). Focal discharges predominantly in the anterior regions, were found in 22 patients (56.8%). Only 7 patients (18.9%) met the diagnostic criteria proposed by Panayiotopoulos in 2005. Conclusions: Few patients meeting the 1989 ILAE diagnostic criteria for CAE meet the new diagnostic criteria proposed by Panayiotopoulos in 2005. The new criteria for CAE are too strict to appropriately classify some patients.

We describe a man with typical absence seizures and generalized tonic-clonic seizures (GTCS) in whom typical Klinefelter syndrome (KS) was diagnosed at the age of 36 years. Epileptic manifestations had onset at the age of 8 years. EEG and clinical data were consistent with juvenile absence epilepsy. This case underscores the little-studied association between epilepsy and KS, which is probably underestimated since KS is often diagnosed in adulthood.

Investigators from University of Chieti and several other centers in Italy conducted a multicenter retrospective 36-month follow-up study of the electroclinical course of epilepsy in all children with typical absence seizures (TAS) starting in the first 3 years of life.

To investigate to which extent lamotrigine (LTG) may be effective and tolerated as a monotherapy for the treatment of newly diagnosed childhood absence seizures and, secondly, to evaluate the efficacy of this drug on the circadian interictal generalized epileptiform discharges, 20 consecutive newly diagnosed patients (five males, 15 females), aged 3–10 years (mean 6.9 years), affected by childhood absence epilepsy, were administered LTG as first-line drug at the initial dose of 0.5 mg/kg/day for 2 weeks, followed by 1.0 mg/kg/day for an additional 2 weeks. Thereafter, doses have been increased in 1-mg/kg/day increments up to 9–12 mg/kg/day in accordance with the clinical response. Each patient underwent an ambulatory (24 h) EEG monitoring before starting LTG therapy (time 0) and during the maintenance period at the end of LTG titration (time 1). After a mean follow-up period of 10.8 months (range 3–28 months), a 100% seizure control was obtained in 11 children (55.5%), a more than 75% seizure decrease was present in four (20%), and a . 50% seizure decrease in five (25%), with a mean LTG dose of 6.2 mg/kg/day (range 1.2–11) in the controlled group. Adverse events were present in three patients (15%); they were generally mild and transient. Our series confirms that LTG monotherapy may control typical childhood absence seizures in about half the children as well as it may decrease interictal generalized spike and wave discharges both in seizure-free and uncontrolled patients. The slow titration phase of the drug due to the risk of the skin rash may eventually reduce compliance. To investigate to which extent lamotrigine (LTG) may be effective and tolerated as a monotherapy for the treatment of newly diagnosed childhood absence seizures and, secondly, to evaluate the efficacy of this drug on the circadian interictal generalized epileptiform discharges, 20 consecutive newly diagnosed patients (five males, 15 females), aged 3-10 years (mean 6.9 years), affected by childhood absence epilepsy, were administered LTG as first-line drug at the initial dose of 0.5 mg/kg/day for 2 weeks, followed by 1.0 mg/kg/ day for an additional 2 weeks. Thereafter, doses have been increased in 1-mg/kg/day increments up to 9-12 mg/kg/day in accordance with the clinical response. Each patient underwent an ambulatory (24 h) EEG monitoring before starting LTG therapy (time 0) and during the maintenance period at the end of LTG titration (time 1). After a mean follow-up period of 10.8 months (range 3-28 months), a 100% seizure control was obtained in 11 children (55.5%), a more than 75% seizure decrease was present in four (20%), and a >50% seizure decrease in five (25%), with a mean LTG dose of 6.2 mg/kg/day (range 1.2-11) in the controlled group. Adverse events were present in three patients (15%); they were generally mild and transient. Our series confirms that LTG monotherapy may control typical childhood absence seizures in about half the children as well as it may decrease interictal generalized spike and wave discharges both in seizure-free and uncontrolled patients. The slow titration phase of the drug due to the risk of the skin rash may eventually reduce compliance. © 2003 Elsevier B.V. All rights reserved.

The aim of this study was to evaluate the effectiveness and accuracy of the "monolog," a pocket-size spike and wave monitor, in patients with typical absence seizures. Two observers were scoring independently and blindly from the monitor the number and duration of the 3 Hz spike-wave discharges from the EEG recordings of 10 selected patients having typical absences. High correlation was found between the two observers' scorings for both the number and the mean duration of events (Spearman's rank correlation (r): 0.9970, P0.001, and 0.9758, P0.001), as well as between each of them and the "monolog" for the mean event duration (r: 0.9848, P0.001, and 0.9788, P0.001). Conversely, a poor correlation was found between each of the observers and the "monolog" for the number of events (r: 0.7121, P = 0.021, and 0.6939, P = 0.026). In conclusion, the "monolog" accurately measured the duration of 3 Hz spike-wave activity; however, it failed to accurately count the number of events that occurred throughout the recordings. We suggest that this device, with appropriate modification to its memory epochs, may be a useful tool in monitoring patients with typical absences.

Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.

Generalised spike-wave discharges (SWD), detectable on the electroencephalogram (EEG), are a hallmark of typical absence seizures. Several mechanisms of transmission have been proposed for SWD seizures including the centrencephalic theory, the corticoreticular theory, and the cortical focus theory [1]. Experimental evidence suggests that seizures rapidly generalise through corticocortical and thalamo-cortical pathways from an excitable cortical ‘focus’ [1]. Further evidence for a cortical focus comes from recent experimental results which show

In this study 8 hours ambulatory EEG monitoring (A/EEG) was performed in 25 outpatients with electroclinical evidence of absence attacks, in order to evaluate the possibility of objective quantification of the epileptic discharges, their distribution during the daytime and their relationship with evident behavioral correlates. A comparison between data obtained by A/EEG and standard EEG (S/EEG) was also made. The results have shown that: 1) it was possible to perform real quantification of the epileptic discharges only through the A/EEG test; 2) the two peaks of a greater incidence of the epileptic discharges corresponded to the execution of relaxing activities and ones requiring a low level of attentiveness; 3) a large number of epileptic generalized discharges did not exhibit a signal pattern like that of a “seizure”, although they were of long duration; and 4) in six patients who showed the normalization of S'/EEG and the disappearance of the absences after one month of valproate therapy, A/EEG revealed the persistence of epileptic discharges. These data demonstrate that A/EEG is a very useful technique for the quantification of paroxysmal discharges and that it may be of importance in the management of this kind of epileptic disorder.

Once-daily ethosuximide was used to treat 10 consecutive children with typical absence seizures. Three patients had gastrointestinal side effects which resolved when the same total daily dose was divided into 2 doses. Two other patients continued to have seizures on ethosuximide, whether given once or twice daily. Five patients had complete seizure control without adverse effects on once-daily ethosuximide.