Cognitive Function and Absence Epilepsy

Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined. In a double-blind, randomized, controlled clinical trial, we compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. Differential drug effects were determined by means of pairwise comparisons. The 453 children who were randomly assigned to treatment with ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P=0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03). Ethosuximide and valproic acid are more effective than lamotrigine in the treatment of childhood absence epilepsy. Ethosuximide is associated with fewer adverse attentional effects. (ClinicalTrials.gov number, NCT00088452.)

Absence seizures during sleep in childhood absence epilepsy: A sign of drug resistance?

Most idiopathic generalized epilepsy (IGE) begins in childhood. Clinicians face many important management decisions for these children; however the existing literature provides little scientific guidance. At the time of presentation, it is unclear how accurately IGE seizures and syndromes are diagnosed and how consistent are the EEG correlates. Investigations beyond EEG are of uncertain value but probably are not needed. Selection of an initial antiepileptic drug (AED) is not based on any adequately powered, blinded, randomized comparative trials; however, reasonable evidence supports the use of valproic acid (VPA), lamotrigine and ethosuccimide as initial treatment for childhood absence epilepsy (CAE). Many large case series suggest the value of VPA for juvenile myoclonic epilepsy (JME) but the relative value of other, newer AEDs has not been established. Once AED treatment is started, it is difficult to establish that absence seizures are completely controlled and the importance of interictal spike-wave discharge remains uncertain. The value of restrictions on the child's activities has not been well studied; however serious accidents appear to be a justifiable concern in children with uncontrolled absence. Assessing the risk from photosensitivity in JME is challenging. The optimal length of treatment for IGE is unclear. There is a high rate of remission in CAE when AEDs are discontinued after 1-2 years of seizure freedom; however, long-term remission in CAE occurs in only 65%. It is usually assumed that treatment for JME is life long, although about 10% appear to have permanent remission in adolescence. Discontinuing AED treatment in JME requires a very individual risk assessment. Long-term social outcome for children with CAE is often unsatisfactory even if the epilepsy remits. The reasons are unclear and successful interventions have not been described. Long-term social outcome for JME has not been adequately described. Further research is needed to justify the direction of many of the necessary management decisions in the diagnosis and treatment of IGE syndromes.

Examine the possible association between long-term seizure outcome in childhood absence epilepsy (CAE) and the initial treatment choice. Children with CAE were prospectively recruited at initial diagnosis and followed in a community-based cohort study. Children presenting with convulsive seizures, significant imaging abnormalities, or who were followed <5years were excluded. Early outcomes included success of initial medication, early remission, and pharmacoresistance. The primary long-term outcome was complete remission: ≥5years both seizure free and medication free. Survival methods were used for analyses. The first medication was ethosuximde (ESM) in 41 (69%) and valproic acid (VPA) in 18 (31%). Initial success rates were 59% (ESM) and 56% (VPA). Early remission and pharmacoresistance were similar in each group. Apart from atypical electroencephalography (EEG) features (61% [VPA], 17% [ESM]), no clinical features varied substantially between the treatment groups. Complete remission occurred in 31 children (76%) treated with ESM and 7 (39%) who received VPA (p=0.007). Children with versus without atypical EEG features were less likely to enter complete remission (50% vs. 71%, p=0.03). In a Cox regression, ESM was associated with a higher rate of complete remission than VPA (hazards ratio [HR]2.5, 95% confidence interval [CI] 1.1-6.0; p=0.03). Atypical EEG features did not independently predict outcome (p=0.15). Five-year and 10-year remission, regardless of continued treatment, occurred more often in children initially treated with ESM versus VPA. These findings are congruent with results of studies in genetic absence models in rats and provide preliminary evidence motivating a hypothesis regarding potential disease-modifying effects of ESM in CAE. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Objective To assess the efficacy and safety of levetiracetam (LEV) monotherapy in children with absence epilepsy.Methods Fifty five children [ 34 males,21 females,aged (8.1 ± 4.8) y ] with typical absence seizures were treated with LEV ( n =25 ) or valproic acid ( VPA,n =30) from Jan 2009 to Jun 2010.Patients were followed up for 1y; the seizure frequency,electroencephalogram (EEG) and side effect were observed at 6th month and 12th month after the initiation of therapy.Results During the follow-up,none had aggravated symptoms of epilepsy.There were no significant differences in seizure frequency(t =0.76,P =0.450; t =0.67,P =0.504),abnormal EEG ( x2 =0.120,P =0.729 ; x2 =0.043,P =0.836 ) and seizure control ( x2 =0.051,P =0.821 ; x2 =0.078,P =0.780) after 6 and 12 months of treatment between two groups.No death or severe side effects were observed; 2 cases (8.0％) in LEV group had mild adverse effect( drowsiness and restlessness)and 2 cases (6.7％ ) in VPA group had weight gain and nausea.Conclusion The results suggest that monotherapy with LEV is effective and safe for treatment of childhood absence epilepsy. Key words: Epilepsy,absence; Therapy; Child

Childhood absence epilepsy patients with cognitive impairment have decreased sleep spindle density

The purpose of the study was to evaluate the incidence of a possible combination of rolandic and absence signs in epileptic children, which remains a subject of controversy. The medical files and electroencephalographic (EEG) records of children with rolandic, childhood absence, and juvenile absence epilepsy were retrospectively analyzed. During the antiepilepsy treatment, 6 of 66 patients with rolandic epilepsy, most of them with initial carbamazepine therapy, had absences and generalized spike-wave discharges of a secondarily generalized type. Five cases of 34 children with childhood absence epilepsy and 3 of 11 patients with juvenile absence epilepsy were identified with an EEG focus of the rolandic type. We considered the likely relation of absence features in rolandic epilepsy to the treatment or to an atypical course. The presence of a rolandic focus in absence epilepsies, however, makes the coincidence of these entirely distinct phenomena, even if very rare, not excluded. Further studies are required to elucidate a probable genetic or functional link between partial and primarily generalized EEG discharges in the idiopathic childhood epilepsies.

Valproate (VPA) is an antiepileptic drug (AED) used for initial monotherapy in treating childhood absence epilepsy (CAE). EEG might be an alternative approach to explore the effects of AEDs on the central nervous system. We performed a comparative analysis of background EEG activity during VPA treatment by using standardized, low-resolution, brain electromagnetic tomography (sLORETA) to explore the effect of VPA in patients with CAE. In 17 children with CAE, non-parametric statistical analyses using sLORETA were performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between the untreated and treated condition. Maximum differences in current density were found in the left inferior frontal gyrus for the delta frequency band (log-F-ratio=-1.390, P>0.05), the left medial frontal gyrus for the theta frequency band (log-F-ratio=-0.940, P>0.05), the left inferior frontal gyrus for the alpha frequency band (log-F-ratio=-0.590, P>0.05), and the left anterior cingulate for the beta frequency band (log-F-ratio=-1.318, P>0.05). However, none of these differences were significant (threshold log-F-ratio=±1.888, P<0.01; threshold log-F-ratio=±1.722, P<0.05). Because EEG background is accepted as normal in CAE, VPA would not be expected to significantly change abnormal thalamocortical oscillations on a normal EEG background. Therefore, our results agree with currently accepted concepts but are not consistent with findings in some previous studies.

Childhood absence epilepsy (CAE), the most common pediatric epilepsy syndrome, is usually treated with valproic acid (VPA) and lamotrigine (LTG) in China. This study aimed to investigate the ictal source locations and functional connectivity (FC) networks between the cortices and thalamus that are related to treatment response. Magnetoencephalography (MEG) data from 25 patients with CAE were recorded at 300Hz and analyzed in 1-30Hz frequency bands. Neuromagnetic sources were volumetrically scanned with accumulated source imaging. The FC networks between the cortices and thalamus were evaluated at the source level through a connectivity analysis. Treatment outcome was assessed after 36-66months following MEG recording. The children with CAE were divided into LTG responder, LTG non-responder, VPA responder and VPA non-responder groups. The ictal source locations and cortico-thalamic FC networks were compared to the treatment response. The ictal source locations in the post-dorsal medial frontal cortex (post-DMFC, including the medial primary motor cortex and the supplementary sensorimotor area) were observed in all LTG non-responders but in all LTG responders. At 1-7Hz, patients with fronto-thalamo-parietal/occipital (F-T-P/O) networks were older than those with fronto-thalamic (F-T) networks or other cortico-thalamic networks (p = 0.000). The duration of seizures in patients with F-T-P/O networks at 1-7Hz was longer than that in patients with F-T networks or other cortico-thalamic networks (p = 0.001). The ictal post-DMFC source localizations suggest that children with CAE might experience initial LTG monotherapy failure. Moreover, the cortico-thalamo-cortical network is associated with age. Finally, the cortico-thalamo-cortical network consists of anterior and posterior cortices and might contribute to the maintenance of discharges.

For several years we have been following patients with intractable, childhood‐onset idiopathic generalised epilepsies with ≥ 3 Hz spike‐wave discharges. Our need to find explanations for their intractability was the starting point for this study. We were interested in identifying characteristics, which would predict intractability; evaluating how these patients were treated and whether polytherapy was useful. We identified patients with ≥ 3 Hz spike‐wave discharges by reviewing EEG reports recorded between 1983 and 1992. Data were collected from medical records and through personal interviews. We identified 82 patients with tentative idiopathic generalised epilepsy. Eleven were excluded. Thirty‐eight patients had childhood absence epilepsy, 18 had juvenile absence epilepsy, 13 had juvenile myoclonic epilepsy and two had eyelid myoclonia with absences: 89.5, 78, 38 and 0% of the patients in each group, respectively, had been seizure free for more than 2 years. Twenty percent of the patients had intractable seizures. All intractable patients with juvenile absence epilepsy had rhythmic, random eyelid blinking and generalised tonic‐clonic seizures. A history of more than ten generalised tonic‐clonic seizures was associated with intractability in juvenile myoclonic patients. Monotherapy with ethosuximide or valproate resulted in seizure control in 65% of patients. Seventeen patients (24%) were treated with polytherapy, six achieved remission. These six patients had childhood absence epilepsy and juvenile absence epilepsy. Positive outcome was found in childhood absence epilepsy and juvenile absence epilepsy. Intractable seizures were more frequent among patients with juvenile myoclonic epilepsy. None of them benefited from polytherapy with conventional anti‐epileptic drugs.

Childhood absence epilepsy (CAE) is a well-defined generalized epilepsy syndrome clinically characterized by frequent absence seizures. The aim of this study was to assess the activity of GABA transaminase (GABA-T) and the kinetic parameters of GABA uptake in platelets from patients with CAE. We studied 13 patients with CAE and eight sex- and age-matched controls. The mean activity of GABA-T was lower in patients with CAE than in controls (1.22+/-0.05 vs. 1.75+/-0.10 micromol/min/kg protein). The capacity of GABA uptake into the platelets was higher in patients using valproate (0.66+/-0.09 micromol/min/kg protein), but not in those using ethosuximide (0.34+/-0.05 micromol/min/kg protein), when compared to controls (0.26+/-0.06 micromol/min/kg protein). The affinity of the transporters was not altered. The observed peripheral alterations may indicate impaired function of brain GABAergic systems in children with absence epilepsy.

Seizures in Epilepsy With Eyelid Myoclonia May Be Provoked by Eye Closure, Not Fixation Removal

Pretreatment electroencephalographic features in patients with childhood absence epilepsy

Absence seizures sometimes present in patients with frontal lobe epilepsy. Cognitive and behavioral problems in patients with absence seizures may be correlated with frontal lobe dysfunction. We report a 15-year-old female patient with absence seizures. She showed learning and behavioral problems such as inattention and impulsivity. We studied serial changes in frontal and prefrontal lobe volume to clarify such correlations among three-dimensional magnetic resonance imaging (MRI). We compared frontal and prefrontal lobe volumes between this patient, the childhood absence epilepsy group ( n = 4, age 8–11 y), and controls ( n = 10, age 6–15 y). Three-dimensional MRI was performed four times in the case (at worsening of absence seizures and 1, 2, and 4 y later) and three times in the childhood absence epilepsy group (at onset and 1 and 2 y later). Even after the complete cessation of seizures, frontal and prefrontal lobe volumes were lower in the case than in patients with childhood absence epilepsy and control subjects. Also, prefrontal-to-frontal lobe volume ratio increased over time in the childhood absence epilepsy and control subjects, whereas its increase was slight in the case. Patients presenting with frontal absence may show prefrontal lobe growth disturbance, which may manifest as poor frontal lobe function.

Increase of frontal delta activity related to perceptual switching