Typical Absence Research Articles

Temporal current-source of spikes suggests initial treatment failure in childhood absence epilepsy

PurposeIn addition to the frontal lobe, the temporal lobe may also be involved in typical absence seizures. However, few studies have addressed the relationship between this involvement and drug responsiveness in childhood absence epilepsy (CAE). In this study, we observed the current-source distribution (CSD) of generalized spike-and-wave discharges (GSWDs) and investigated the relationship between temporal lobe involvement in the CSD and responsiveness to initial antiepileptic drug (AED) in CAE. MethodSeventeen consecutive patients with CAE were retrospectively enrolled in the study. Patients were divided into an initial-response group and an initial-failure group, according to their responsiveness to the initial AED treatment. For each patient, the spike peak CSD of an averaged GSWD was obtained from the initial electroencephalogram. We compared the incidence of temporal involvement in the CSD between the two groups. We also compared clinical variables, including age of onset, gender, type and dose of first AED, time to cessation of clinical seizures, and seizure-free status. ResultsThe initial-response and initial-failure groups contained 12 and five patients, respectively. Temporal lobe involvement was more frequent (80% vs. 17%, p=0.03), and time to cessation of clinical seizures was more prolonged (median 2.5 months vs. 8 months, p<0.01) in the initial-failure than in the initial-response group. None of the other variables studied differed between groups. ConclusionInitial AED failure was associated with temporal involvement in the CSD of CAE patients. This electrophysiological information may be helpful in clinical practice by estimating the efficacy of initial AED treatment in AED-naïve CAE patients in advance.

TYPICAL ABSENCES: RESULTS OF OWN INVESTIGATIONS

Typical absences (TA) are brief primary generalized epileptic seizures characterized by sudden onset and termination. According to their definition, absences consist of impairment of consciousness that is synchronously accompanied by electroencephalographic (EEG) changes as generalized spike–slow wave discharges of 3 or more Hz. The authors conducted an investigation of 1261 patients with different forms of epilepsy with onset of seizures from the first days of life to the age of 18 years. The patients were followed up from 1990 to 2010. Absence seizures were detected in 231 patients, which accounts for 18.3 % of all the epileptic patients. TA were found in 102 patients, which constitutes 8.1 % of all cases of epilepsy with onset of seizures beyond the age of 18 years. The paper provides a detailed analysis of a group of patients with TA in terms of anamnestic, clinical, electroencephalographic, and neuroimaging features and the results of therapy with antiepileptic drugs (AEDs). The age of onset of TA-associated epilepsy was from 9 months to 17 years (mean 9.4 ± 4.06 years). The disease occurred most frequently in young school-age children (41.2 %). Isolated TA as the only type of seizures were observed in the clinical picture of 28 (27.5 %) patients. TA were concurrent with other types of seizures in other cases. The investigators have identified 4 types of seizures which TA (generalized convulsions, myoclonic seizures, febrile seizures, and eyelid myoclonia) may be concurrent with. Neuroimaging stated there were no brain changes in 85.3 % of TA-associated epilepsy cases. Moderate diffuse subatrophic changes were detected in other cases (14.7 %). Local cerebral structural abnormalities were absent. The use of antiepileptic therapy as both monotherapy and polytherapy using different combinations showed the high efficacy of AEDs. Complete remission was achieved in 84.3 % of TA-associated epilepsy cases. An AED-induced reduction in the frequency of seizures was observed in 15.7 % of the patients. No one case – without effect. The greatest success in relieving seizures was seen in juvenile myoclonic epilepsy; childhood absence epilepsy was intermediate; the lowest percentage of remission was noted in juvenile absence epilepsy. The most effective drugs were valproic acid and ethosuximide used both alone and in combination. Lamotrigine, topiramate, and levetiracetam were used as part of combination therapy.

Stro-1/CD44 as putative human myometrial and fibroid stem cell markers

To identify and characterize myometrial/fibroid stem cells by specific stem cell markers in human myometrium, and to better understand the stem cell contribution in the development of uterine fibroids. Prospective, experimental human and animal study. University research laboratory. Women undergoing hysterectomy for treatment of symptomatic uterine fibroids and female NOD/SCID/IL-2Rγ(null) mice. Identification and isolation of stem cells from human fibroids and adjacent myometrium tissues using Stro-1/CD44-specific surface markers. Flow cytometry, semiquantitative polymerase chain reaction, clonogenicity assays, cell culture, molecular analysis, immunocyto-histochemistry, invitro differentiation, and xenotransplantation assays. Using Stro-1/CD44 surface markers, we were able to isolate stem cells from adjacent myometrium and human fibroid tissues. The undifferentiated status of isolated cells was confirmed by the expression of ABCG2 transporter, as well as additional stem cell markers OCT4, NANOG, and GDB3, and the low expression of steroid receptors ERα and PR-A/PR-B. Mesodermal cell origin was established by the presence of typical mesenchymal markers (CD90, CD105, and CD73) and absence of hematopoietic stem cell markers (CD34, CD45), and confirmed by the ability of these cells to differentiate invitro into adipocytes, osteocytes, and chondrocytes. Finally, their functional capability to form fibroid-like lesions was established in a xenotransplantation mouse model. The injected cells labeled with superparamagnetic iron oxide were tracked by both magnetic resonance imaging and fluorescence imaging, thus demonstrating the regenerative potential of putative fibroid stem cells invivo. We have demonstrated that Stro-1/CD44 can be used as specific surface markers to enrich a subpopulation of myometrial/fibroids cells, exhibiting key features of stem/progenitor cells. These findings offer a useful tool to better understand the initiation of uterine fibroids, and may lead to the establishment of effective therapeutic options.

P48 – 2876: The evaluation of the frontal lobe function in the patients with absence epilepsy

Objective Based on earlier studies, CAE has been considered as a benign disorder with relatively easily attained seizure control and minimal involvement of cognition and behavior. However, more recent outcome studies report a varying rate of seizure control, as well as learning and cognitive difficulties. The aim of this study is the evaluation of neurocognitive function, especially frontal lobe, in the patients with typical absence epilepsy. Methods Thirty-eight (19 healthy children and 19 patients) participants were enrolled. Neurocognitive function tests such as Serial Digit Learning Test, Wisconsin Card Sorting Test, Visual Aural Digit Span Test and STROOP Test were performed to all participants. Results There was a significant difference between the groups according to Serial Digit Learning Test (SDLT) and the subgroup of Wisconsin Card Sorting Test. As for the WCST performance, there was significant difference in categories achieved, difficulty of maintaining set, perseverative errors, and perseverative responses between patient and control groups (p=0.037, p=0.010, p=0.011). In Serial Digit Learning Test and in the non-perseverative error subgroup of WCST performance, there was a significant difference in the patient group whose seizures started before the age 6 (p=0.029, p=0.041). As for the Visual-Aural Digit Span Test performance, there was a significant difference between the groups when compared to the duration response to drug treatment in categories achieved, aural-oral, visual-oral, aural-written, and visual-written. (p=0.010, p=0.025, p=0.012, p=0.034). Conclusion Long-term risk of learning impairments, failure in executive abilities, short-term memory and attention disorders can occur in children with absence epilepsy, especially in patients whose seizure started before the age of 7 years not responding to single drug, and the duration of response to drug was longer than 6 months. Our results highlight potentially detrimental effect of absence seizures on cognition.

Epileptic activity during early postnatal life in the AY-9944 model of atypical absence epilepsy

Atypical absence epilepsy (AAE) is an intractable disorder characterized by slow spike-and-wave discharges in electroencephalograms (EEGs) and accompanied by severe cognitive dysfunction and neurodevelopmental or neurological deficits in humans. Administration of the cholesterol biosynthesis inhibitor AY-9944 (AY) during the postnatal developmental period induces AAE in animals; however, the neural mechanism of seizure development remains largely unknown. In this study, we characterized the cellular manifestations of AY-induced AAE in the mouse. Treatment of brain slices with AY increased membrane excitability of hippocampal CA1 neurons. AY treatment also increased input resistance of CA1 neurons during early postnatal days (PND) 5–10. However, these effects were not observed during late PND (14–21) or in adulthood (7–10 weeks). Notably, AY treatment elicited paroxysmal depolarizing shift (PDS)-like epileptiform discharges during the early postnatal period, but not during late PND or in adults. The PDS-like events were not compromised by application of glutamate or GABA receptor antagonists. However, the PDS-like events were abolished by blockage of voltage-gated Na+ channels. Hippocampal neurons isolated from an in vivo AY model of AAE showed similar PDS-like epileptiform discharges. Further, AY-treated neurons from T-type Ca2+ channel α1G knockout (Cav3.1−/−) mice, which do not exhibit typical absence seizures, showed similar PDS-like epileptiform discharges. These results demonstrate that PDS-like epileptiform discharges during the early postnatal period are dependent upon Na+ channels and are involved in the generation of AY-induced AAE, which is distinct from typical absence epilepsy. Our findings may aid our understanding of the pathophysiological mechanisms of clinical AAE in individuals, such as those with Lennox–Gastaut syndrome.

Role of Laterodorsal Thalamic Nucleus during Absence Seizure Attacks

Introduction: A typical absence epilepsy is a type of nonconvulsive and generalized epilepsy. The main feature of these attacks is a sudden brief impairment of consciousness. The disturbances in thalamocortical loop play an important role in pathogenesis of absence seizures. However, it is not clear that which part of this network triggers the seizure. This study was aimed to investigate the role of latrodorsal (LD) thalamic neurons during spike and wave discharges (SWDs) in WAG/Rij rats, as the most valid animal model of absence epilepsy. Materials and Methods: Single unit activities in the LD thalamic nucleus and electrocorticogram of somatosensory cortex were simultaneously recorded in six-month-old WAG/Rij rats. Results: During SWDs, unit activity in the LD thalamic nucleus showed burstlike discharges, which were started before the peak component of SWDs. In SWD-free periods, burst like activity in the LD was reduced. Conclusion: Our findings suggest that the burst firing of LD may stimulate the neocortex to exhibit SWDs. It can be concluded that inhibition of

Smooth muscle and adenoma-like renal tumor: a previously unreported variant of mixed epithelial stromal tumor or a distinctive renal neoplasm?

We describe 6 cases of a biphasic renal neoplasm, which we designate smooth muscle and adenoma-like renal tumor, which do not cleanly fit any category as currently defined. There were 4 females and 2 males (age, 27-70 years); neither male had a history of hormone exposure. All 5 neoplasms with available history were discovered incidentally on imaging studies with sizes ranging from 4 to 20 cm. The stroma was composed of smooth muscle fascicles alternating with looser, edematous areas; none of the cases contained ovarian-like stroma. The complex but cytologically benign epithelial component consisted of tubulopapillary nodules, branching tubules, clefts, and large cysts. The stroma of all of the cases labeled diffusely for desmin. Estrogen receptor labeling was absent in 4 cases with only minimal (<10%) weak labeling in the remaining 2. The epithelial component of each case labeled diffusely for cytokeratin 7 and was patchy for α-methyl-CoA racemase (P504S). Carbonic anhydrase IX, HMB45, WT-1, and inhibin were negative. None of the 5 cases tested demonstrated trisomies of chromosome 7 or 17 by fluorescence in situ hybridization. Two patients with significant follow-up are disease free at 18.5 and 2.5 years. Smooth muscle and adenoma-like renal tumor could potentially represent a variant of mixed epithelial stromal tumor, which would expand its reported spectrum. However, the absence of clinical history of hormone exposure, predominance of smooth muscle with lack of ovarian-like stroma, prominence of epithelial nodules, and typical absence of estrogen receptor labeling suggest that it may represent a distinct entity.

Pyroclasts of the First Phases of the Explosive-Effusive PCCVC Volcanic Eruption: Physicochemical Analysis

The morphology, texture, grain size and other physicochemical characteristics of pyroclastic material from the first phases of the Puyehue-Cordon Caulle volcanic complex (PCCVC) eruption, (Southern Andes, Chile), can be associated to the model recently reported for the magma storage and its ascent conditions. The eruption started June 4th 2011, and the studied volcanic material corresponds to that collected in Argentine territory at different distances from the source, between 4 and 12 June 2011. The explosive-effusive volcanic process of the first days occurred with the simultaneous emplacement of lava flows and the venting of pyroclastic material, ejecting two well differentiated types of particles. The more abundant was constituted by rhyolitic and light color pumice fragments, characterized by a typical vesicular texture, easy fragmentation and absence of occluded crystalline phases. Particles found in minor proportion were dark color, different in shape and texture and rich in Fe and Ti. They seemed to be more effective for the interaction with emitted gases in the upper part of the column, for this reason, they appeared partially covered by condensation products. The ascent conditions of the magma affected its rheological behavior through variations in the degassing, viscosity and fragmentation. On the other hand, distance to the source, depositional time, volcanic evolution and environmental conditions are factors that affect the chemical composition of collected ash. So, the SiO2/FeO ratio not only increases with the distance but also with the deposition time and volcanic activity. The work was done with the aid of several techniques such as a laser-sediment analyzer, X-ray diffraction (XRD), chemical analysis (bulk and surface), SEM microscopy and Raman “microprobe” spectroscopy. On the other hand, the physicochemical behavior of the pyroclastic material allows us to suggest eventual applications.

Epilepsia de ausencia juvenil. Evaluación neuropsicológica de dos casos

Introducción: Las epilepsias constituyen trastornos de la función neuronal expresados en crisis de episodios limitados causadas por descargas anormales de grupos de neuronas. La epilepsia de ausencia juvenil inicia entre los 10 y 17 años, con ausencias típicas y en ocasiones crisis tónico-clónicas. Ambos sexos son igualmente afectados. El electroencefalograma (EEG) intercrítico presenta descargas de punta-onda de 3 Hz con buena respuesta al medicamento. Las evaluaciones neuropsicológicas permiten determinar la presencia de cambios cognoscitivos y comportamentales. Material y métodos: Estudio observacional, descriptivo, transversal, prospectivo. Se evaluaron dos estudiantes de la Licenciatura en Psicología (casos A y B), de 19 años de edad, de lateralidad diestra, sexo femenino. En ambos casos se reportaron crisis de ausencia con inicio en la adolescencia; el caso B presentaba además crisis tónico-clónicas. Ambas se encontraban tomando medicamento en el momento de la evaluación. En forma individual, en un cubículo bien iluminado, libre de distractores, se aplicaron en dos sesiones de 45 minutos en promedio la evaluación neuropsicológica breve en español (NEUROPSI), el test de clasificación de Wisconsin versión computarizada (WISCONPC) y la escala de somnolencia Epworth. Resultados: En NEUROPSI, el caso A, obtuvo puntaje total de 118 (normal alto) y el caso B, 106 (normal) con dificultades en atención, evocación de estímulos verbales y comprensión lectora. En WISCONPC, el caso A completó seis categorías, mientras que el B completó dos, presentando incapacidad para mantener la organización. En la escala Epworth, el caso B reportó no dormir suficiente. Discusión y conclusiones: Las evaluaciones neuropsicológicas nos permitieron conocer el estado actual de los procesos cognoscitivos de los casos evaluados e indicar estrategias de corrección en los procesos observados con dificultades.

Control of absence seizures induced by the pathways connected to SRN in corticothalamic system

The cerebral cortex, thalamus and basal ganglia together form an important network in the brain, which is closely related to several nerve diseases, such as parkinson disease, epilepsy seizure and so on. Absence seizure can be characterized by 2-4 Hz oscillatory activity, and it can be induced by abnormal interactions between the cerebral cortex and thalamus. Many experimental results have also shown that basal ganglia are a key neural structure, which closely links the corticothalamic system in the brain. Presently, we use a corticothalamic-basal ganglia model to study which pathways in corticothalamic system can induce absence seizures and how these oscillatory activities can be controlled by projections from the substantia nigra pars reticulata (SNr) to the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of the thalamus. By tuning the projection strength of the pathway "Excitatory pyramidal cortex-SRN", "SRN-Excitatory pyramidal cortex" and "SRN-TRN" respectively, different firing states including absence seizures can appear. This indicates that absence seizures can be induced by tuning the connection strength of the considered pathway. In addition, typical absence epilepsy seizure state "spike-and-slow wave discharges" can be controlled by adjusting the activation level of the SNr as the pathways SNr-SRN and SNr-TRN open independently or together. Our results emphasize the importance of basal ganglia in controlling absence seizures in the corticothalamic system, and can provide a potential idea for the clinical treatment.

Time-scale uncertainty of abrupt events in the geologic record arising from unsteady sedimentation

Defining the time scale of abrupt events in the stratigraphic record is a primary goal of high-resolution paleoclimate analysis. A significant hurdle in this endeavor is that abrupt, i.e., millennial and submillennial, events in deep time can rarely be temporally constrained accurately owing to the typical absence of high-precision age control at the scale of the events. Instead, the duration of abrupt events is commonly estimated via the linear partitioning of time between age control points (e.g., defined using astronomical cycles or radiometric dates) that bracket the event and span longer time intervals. The flaw with this approach is that sedimentation is an unsteady process and does not proceed linearly with time. Here a numerical model, parameterized by geologic data, is used to quantify theoretical time-scale uncertainties that result from unsteady sedimentation. This work demonstrates that the duration of assumed millennial events estimated via a linear partitioning approach may be significantly in error, even in complete, astronomically calibrated and unbioturbated successions best suited to the study of abrupt paleoclimate change. The uncertainties established in this study are largely a function of the precise statistical properties of the sedimentation process, properties that are difficult to constrain empirically, particularly over short time spans. Nevertheless, this study illustrates how unsteady sedimentation sets an important limit on the attainable temporal resolution of the stratigraphic record, with consequent implications for defining accurately the rates and durations of rapid events in Earth history.

First-drug treatment failures in children with typical absence epilepsy.

Childhood absence epilepsy (CAE) is a well-known syndrome with onset in middle childhood and is characterized by multiple typical absences per day. Pharmacological treatment is specific and usually successful with a single medication. The goal of the study was to assess on risk factors associated with failure to respond to the initial antiepileptic drug (AED). Fifty-two children with CAE were enrolled. Predictive factors were analyzed by survival methods. Among 52 patients, 32 patients (61.5%) were girls and the remaining 20 (38.5%) were boys and the mean age at the seizure onset was 6.5±1.78 years old (3-11.5 years). Of the 52 patients, 42 (80.8%) were treated relatively successfully with the first AED treatment (Group A), and 10 (19.2%) were not responsed (Group B). Age of seizure onset, coexisting other types of seizures, and photoconvulsive EEG response were significantly associated with failure risk according to univariate analysis. In the multivariate analysis, only photoconvulsive EEG response was the risk factor influencing poor response to initial AED treatment. Factors predicting failure to respond to the AED were age of seizure onset, coexisting other types of seizures, and photoconvulsive EEG response in children with CAE.

Abnormal response to photic stimulation in juvenile myoclonic epilepsy: an EEG-fMRI study.

Juvenile myoclonic epilepsy (JME) is a young-onset electroclinical syndrome, characterized by myoclonic, generalized tonic-clonic, and possibly typical absence seizures. Interictal electroencephalography (EEG) displays 3-6 Hz spike/polyspike and wave pattern. Photosensitivity is common. Our aim was to explore the blood oxygen level-dependent (BOLD) response evoked by a highly provocative photic stimulus in a cohort of people with JME compared to a group of nonphotosensitive healthy controls, and to investigate the hemodynamic phenomena seen in patients with photosensitive JME. We studied 13 JME patients and 18 healthy controls using EEG-functional magnetic resonance imaging (fMRI) performed during low luminance intermittent photic stimulation (IPS). The BOLD response to IPS was investigated both in JME and control groups. In photosensitive JME subjects, we also performed a dynamic evaluation of BOLD signal changes evoked by the photoparoxysmal response (PPR) in a time frame ranging from 10 s before the onset of the EEG paroxysm up until 10 s afterward. The IPS evoked a positive BOLD response in striate and extrastriate visual areas, which was less in JME patients than in controls. Moreover, people with JME had a reduced positive BOLD response in the frontoparietal areas and putamen but a stronger negative BOLD response in the primary sensorimotor cortex (SM1) and in cortical regions belonging to the default mode network (DMN). In JME, the dynamic evaluation of BOLD signal changes related to PPR revealed an early positive response in the putamen and SM1, followed by BOLD signal decrements in the putamen, caudate nuclei, thalami, and SM1. Our results confirm the hypothesis that people with JME might have an altered interaction between the motor circuit and other neuronal networks, with prominent involvement of basal ganglia circuitry. The PPR could be a final expression of pathogenic phenomena occurring in the striato-thalamocortical system, possibly a core feature of system epilepsy JME.

Long-term follow-up of adult patients with genetic generalized epilepsy with typical absence seizures and generalized paroxysmal fast activity in their EEG

PurposeGeneralized 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. MethodsWe 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. ResultsThe 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. ConclusionOur 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.

Journal club: pretreatment EEG in childhood absence epilepsy.

Childhood absence epilepsy (CAE) is defined by absence seizures in a normally developing child, with onset between 4 and 10 years of age.(1) Typical absence seizures consist of behavioral arrest with or without automatisms, usually last 30-60 seconds, and demonstrate a characteristic 3-Hz generalized spike-wave (GSW) pattern on EEG, often in response to hyperventilation.(2) Children may have hundreds of episodes daily, many of them subclinical, which can impair sustained attention and memory processing. There is a strong association between CAE and disorders of attention and executive function. This association persists even when seizures are well-controlled. An underlying structural or functional abnormality of the brain has been postulated to explain both observations.(3,4) This article by Dlugos et al.(5) is a post hoc analysis of a randomized, double-blinded trial(6) that seeks to characterize the relationship between EEG characteristics prior to treatment, measures of attention, and the outcome of initial antiepileptic treatment.

Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence

Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. Besides the direct coupling, anatomical evidence indicates that the cerebral cortex and thalamus also communicate indirectly through an important intermediate bridge–basal ganglia. It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. Using a biophysically based model, we demonstrate here that the typical absence seizure activities can be controlled and modulated by the direct GABAergic projections from the substantia nigra pars reticulata (SNr) to either the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of thalamus, through different biophysical mechanisms. Under certain conditions, these two types of seizure control are observed to coexist in the same network. More importantly, due to the competition between the inhibitory SNr-TRN and SNr-SRN pathways, we find that both decreasing and increasing the activation of SNr neurons from the normal level may considerably suppress the generation of spike-and-slow wave discharges in the coexistence region. Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder.

Ezogabine treatment of childhood absence epilepsy

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 50mg daily was added. The dose was slowly increased and once a total dose of only 200mg/day was reached, she became seizure-free for three months. After subsequently discontinuing zonisamide, absence seizures returned. Further increasing the ezogabine to 400mg/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.

Dynamic magnetic source imaging of absence seizure initialization and propagation: A magnetoencephalography study

The present study aims to determine the initialization and propagation of typical absence seizures using magnetoencephalography (MEG). Fourteen drug-naïve children with childhood absence epilepsy (CAE) were studied using a 275-Channel MEG system. The spectral signatures of epileptic activity were assessed using Morlet continuous wavelet transform. Magnetic sources were volumetrically localized using dynamic magnetic source imaging (dMSI) with a slide window at a millisecond temporal resolution. The initial portion of ictal activity was predominantly located to the left frontal and posterior cortices. The frontal sources were in the left medial prefrontal cortex (MPFC), the pre-supplementary motor area (pre-SMA), the primary motor cortex, and the lateral prefrontal cortex. The posterior cortical sources were predominantly localized to the left precuneus (pC) and the medial occipital cortices (MOC). The ictal activity after the initialization showed involvement of the MPFC and pC of all patients (14/14) and recursive propagation between the frontal (MPFC) and posterior cortices (pC and MOC) via either the medial portion of the brain (9/14) or the thalamus (5/14), respectively. The left frontal and posterior (pC and MOC) cortices play a key role in the initialization of epileptic activity in absence seizures. The thalamus plays a key role in the propagation of absence seizures between the frontal and posterior cortical sources. Considering the MPFC and pC are the nodes of the default mode network (DMN), our results support involvement of the DMN in absence seizures.

Is there such a thing as "generalized" epilepsy?

The distinction between generalized and partial epilepsies is probably one, if not the most, pregnant assertions in modern epileptology. Both absence and generalized tonic-clonic seizures, the prototypic seizures found in generalized epilepsies, are classically seen as the result of a rapid, synchronous recruitment of neuronal networks resulting in impairment of consciousness and/or convulsive semiology. The term generalized also refers to electroencephalographic presentation, with bilateral, synchronous activity, such as the classical 3 Hz spike and wave discharges of typical absence epilepsy. However, findings obtained from electrophysiological and functional imaging studies over the last few years, contradict this view, showing a rather focal onset for most of the so-called generalized seizure types. Therefore, we ask here the question whether "generalized epilepsy" does indeed exist.

Calcium channel antibodies in patients with absence epilepsy

Autoimmunity has aroused interest in the last years as a contributory mechanism of epilepsy, especially in epilepsies with unknown cause or therapy resistance. Since the relationship of absence epilepsy (AE) with calcium channels is well established, we aimed to investigate related antibodies in patients diagnosed with AE. Consecutive patients with typical absence seizures having either childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) with generalized spike and wave discharges on electroencephalography (EEG) were included after their consent. The patients were diagnosed according to the International League Against Epilepsy (ILAE) 2010 criteria. Antibodies against P-Q type voltage gated calcium channels (VGCC) and T-type VGCC subunit Cav3.2 (encoded by the CACNA1H gene) were investigated by RIA and ELISA, respectively. We searched for these antibodies in 32 patients with AE and 53 patients with focal epilepsy of unknown cause (FEOUC) as the disease control group; furthermore, 30 healthy persons served as the healthy controls. Eleven patients (34.3%) with AE had CAE and the remaining patients had JAE. Only a 47-year-old female FEOUC patient, who also had systemic lupus erythematosus with normal MRI scans showed antibodies against P-Q type VGCC, whereas no antibody positivity could be found in other FEOUC and AE patients and healthy controls. Our results might suggest that calcium channel antibodies do not play an important role in the pathophysiology of AE. Further studies with larger groups of other epileptic syndromes are needed to confirm our results.