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Background: Levetiracetam is prescribed for a broad spectrum of seizure types but does not have a specific indication for absence epilepsy. We hypothesized that levetiracetam is commonly prescribed for children with absence epilepsies and evaluated the efficacy of this medication for absence epilepsy treatment in clinical practice. We also hypothesized that electroencephalographic (EEG) findings could help predict levetiracetam efficacy. Methods: We reviewed the charts of all patients treated for new-onset absence epilepsies at our pediatric neurology clinic between January 2011 and January 2016. Among 158 children diagnosed with absence epilepsies, 72 were treated with levetiracetam. Results: Levetiracetam was discontinued in 74% (n = 53/72) because of incomplete seizure control (59%, n = 35/72) and/or intolerable side effects (41%, n = 24/72) after a median 8.5 months (interquartile range 2, 17 months). Among patients for whom levetiracetam was effective, 44% (n = 8/18) had polyspikes on their initial EEG, versus 27% (n = 14/52) of patients for whom levetiracetam was discontinued ( P = .17). The maximal prescribed dose was lower for children in whom levetiracetam was effective (29 ± 13 mg/kg/d) than those for whom levetiracetam failed (42 ± 20 mg/kg/d; P = .005). Conclusion: In routine clinical practice, levetiracetam is often chosen for patients with absence seizures. However, only about one-quarter of children with absence epilepsy in this study became seizure free with levetiracetam. When effective, levetiracetam can control absence epilepsy at a relatively low dose. Lack of seizure control requiring continued dose escalation should prompt early consideration of a therapeutic medication transition.

Objective: To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy (GE) with second- and third-generation antiepileptic drugs (AEDs). Methods: The 2004 AAN criteria was used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic–clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. Recommendations: Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years with new-onset focal epilepsy. Unless there are compelling adverse-effect–related concerns, ethosuximide (ETS) or valproic acid (VPA) should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (Level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.

Objective: To update the 2004 American Academy of Neurology (AAN) guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs). Methods: 2004 criteria were used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Forty-two articles were included. Recommendations: The following are established as effective to reduce seizure frequency (Level A): immediate-release pregabalin and perampanel for TR adult focal epilepsy (TRAFE); vigabatrin for TRAFE (not first-line treatment; rufinamide for Lennox–Gastuat syndrome (LGS) (add-on therapy). The following should be considered to decrease seizure frequency (Level B): lacosamide, eslicarbazepine, and extended-release topiramate for TRAFE (ezogabine production discontinued); immediate- and extended-release lamotrigine for generalized epilepsy with TR generalized tonic–clonic (GTC) seizures in adults; levetiracetam (add-on therapy) for TR childhood focal epilepsy (TRCFE) (1 month to 16 years), TR GTC seizures, and TR juvenile myoclonic epilepsy; clobazam for LGS (add-on therapy); zonisamide for TRCFE (6–17 years); oxcarbazepine for TRCFE (1 month to 4 years). The text presents Level C recommendations. AED selection depends on seizure/syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. This evidence-based assessment informs AED prescription guidelines for TR epilepsy and indicates seizure types and syndromes needing more evidence. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years of age and perampanel as monotherapy received FDA approval.

Background:Sodium valproate (VPA) is considered as the drug of choice for the treatment of generalized epilepsy in children. Sodium Valproate may be hepatotoxic.Aim:To assess the level of derangement of liver enzymes in children with epilepsy on treatment with sodium valproate.Methods:A cohort study. One hundred fifty-three children, comprising 51 with epilepsy on treatment with VPA (group I), 51 with epilepsy on treatment with other antiepileptic drugs (AEDs) but not VPA (group II), and 51 with nonconvulsive disorders (group III) had liver function tests performed for them. Data were analyzed by SPSS version 23.0.Results:There were 85 males and 68 females, aged 6 months to 14 years (median = 7.0 years). There was no significant difference in the mean plasma levels of alanine transaminase (ALT), alkaline phosphatase, and gamma glutamyl transferase across the three groups of children. The mean aspartate transaminase level was significantly higher in children in group III. There was a statistically significant negative correlation between the duration of AED therapy and the mean serum level of AST ( r = −0.266, P = 0.016). The serum ALT level showed a statistically significant positive correlation with the duration of AED therapy ( r = 0.268, P = 0.015).Conclusion:Sodium valproate monotherapy does not appear to be associated with significant hepatotoxicity in children in our cohort.

Rufinamide (RFD) is a novel drug that was recently approved as an adjunctive treatment for Lennox-Gastaut syndrome. Despite its reported effectiveness in generalized seizures (tonic, atonic, or tonic-clonic) in this syndrome, few data on its use in idiopathic generalized epilepsy are available. Indeed, the scientific evidence to date is limited to anecdotal cases or isolated clinical experiences. We report an uncommon, though paradigmatic, case of a woman affected by juvenile absence epilepsy (JAE) who, following a prolonged seizure-freedom period and the consequent withdrawal of valproate, presented a seizure relapse accompanied by a worsening in her electroclinical pattern. In view of this atypical evolution of JAE, characterized by drug-resistant seizures (absence and generalized tonic-clonic) and the progressive increase in electroencephalographic (EEG) abnormalities, several antiepileptic drugs were used, though to no benefit. The use of RFD instead led to a gradual control of the seizures and normalization of the EEG findings. In addition to this clinical experience, we briefly review the literature on the use of RFD in refractory generalized epilepsy.

The coexistence of focal and generalized epilepsy is rare. We report on a 17-year-old male with drug-resistant focal epilepsy and idiopathic generalized epilepsy (IGE). He began to experience generalized tonic-clonic seizures (GTCS) at the age of 3 years, with a good response to phenobarbital. At the age of 14 years, he began to experience complex partial seizures (CPS). Video-electroencephalography (video-EEG) telemetry showed the coexistence of right temporal spikes and bursts of generalized spike-wave (GSW). The ictal EEG showed a unique EEG pattern characterized by a 4- to 5-second burst of GSW followed by rhythmic delta activity over the right temporal region. A magnetic resonance image (MRI) showed right hippocampal sclerosis. The patient underwent a right temporal lobectomy that significantly improved his seizure control. He was rendered seizure free of the complex partial seizures and improvement of the GTCS. This case illustrates a very uncommon ictal EEG pattern, and shows that the decision for surgery in patients with focal drug-resistant epilepsy should not be affected by coexistent generalized epilepsy.

The corpus callosum is the main band of interhemispheric axonal fibers in the human brain. Corpus callosum agenesis has widely varying symptoms, mainly associated with epilepsy, cognitive failure, and different neuropsychiatric disorders. Our case of corpus callosum agenesis includes eyelid myoclonia with absences. In the literature, there is no reported case of this combination. We report this case because it is rare, and relevant for the understanding of interhemispheric communications, based on our electrophysiological findings.

Postictal headache (PIH), although it occurs in 34–59% of epilepsy patients, has not been adequately studied. This study aims to describe clinical characteristics and associations of PIH in generalised epilepsy in a South African tertiary neurology clinic. Methods: Two-hundred consecutive adults with generalised epilepsy underwent semi-structured interviews, dividing them into study (with PIH) and control patients (no PIH), and data was statistically analysed. Results: PIH occurred in 104/200, with 63% having headache after every seizure. Pain duration was 4–24 hours in 43% and pain intensity severe in 55%. The criteria of the International Headache Society (2004), International Classification of Headache Disorders, second edition (ICHD-II) classified 47% as migraine, 38% tension-type and 15% unclassified (but 13% probable migaine). Self-medication occurred in 81% and interictal headache was significantly associated with PIH—present in 64% of study patients versus 5% of control patients. Conclusion: PIH occurs commonly in generalised epilepsy, mostly as migraine headache, with interictal headache a specific risk factor. PIH is underdiagnosed and undertreated, leading to self-medication. Optimal management should be elucidated in future studies.

Epilepsy accounts for 0.5% of the global burden of disease, and primary prevention of epilepsy represents one of the three 2007 NINDS Epilepsy Research Benchmarks. In the past decade, efforts to understand and intervene in the process of epileptogenesis have yielded fruitful preventative strategies in animal models.This article reviews the current understanding of epileptogenesis, introduces the concept of a “critical period” for epileptogenesis, and examines strategies for epilepsy prevention in animal models of both acquired and genetic epilepsies. We discuss specific animal models, which may yield important insights into epilepsy prevention including kindling, poststatus epilepticus, prolonged febrile seizures, traumatic brain injury, hypoxia, the tuberous sclerosis mouse model, and the WAG/Rij rat model of primary generalized epilepsy. Hopefully, further investigation of antiepileptogenesis in animal models will soon enable human therapeutic trials to be initiated, leading to long-term epilepsy prevention and improved patient quality of life.

Mutations in ligand-gated ion channel genes associated with idiopathic generalized epilepsies have been reported in excitatory acetylcholine receptor α4 and β2 subunit genes linked to autosomal dominant nocturnal frontal lobe epilepsy and in inhibitory GABAA receptor α1, β3, γ2, and δ subunit genes associated with childhood absence epilepsy, juvenile myoclonic epilepsy, pure febrile seizures, generalized epilepsy with febrile seizures plus, and generalized epilepsy with tonic–clonic seizures. Recent studies suggest that these mutations alter receptor function or biogenesis, including impaired receptor subunit messenger RNA stability, receptor sub-unit protein folding and stability, receptor assembly, and receptor trafficking.

Absence epilepsy is a form of generalized epilepsy commonly seen in children. The clinician is often presented with a patient whose electroencephalogram does not fit the typical absence pattern. The purpose of this study is to more closely examine both typical and atypical absence variants and their outcome. A retrospective chart review was performed on children diagnosed with absence epilepsy over the past 5 years at the University of Alberta. A total of 119 patients were reviewed. Patients were classified with typical or atypical absence seizures following International League Against Epilepsy criteria and electroencephalography (EEG) characteristics. Clinical seizure characteristics, magnetic resonance imaging (MRI), initial response to treatment, and outcome were examined. Seizure characteristics were similar in both the typical and atypical absence groups. Aura, complex automatisms, changes in tone, and incontinence were seen in both groups, although status epilepticus was found only in the atypical group. Associated comorbid conditions such as attention-deficit hyperactivity disorder (ADHD), learning disorders, and enuresis were found equally in both groups. Developmental delay was found more often in the atypical group. Of the typical group, 83% responded to an initial antiepileptic drug (either valproic acid or ethosuximide), whereas only 51% of the atypical group came under control. Remission at 2 years however, was similar between groups, with 76% of the typical group and 71% of the atypical group completely seizure free. Absence seizures in childhood, both typical and atypical, share similar clinical and electroencephalographic features and appear to be part of a continuum. Associated comorbid features such as ADHD, learning disorders, and developmental delay are also seen in both groups. The outcome for both types is excellent, although the atypical variants may be initially more difficult to control.

Data for children 1 month to 15 years of age at the time of diagnosis of epilepsy were recorded from the children's hospital “Virgen del Camino” in Pamplona (Spain) from January to December 2005. International League Against Epilepsy criteria were used for diagnoses. A total of 365 children were recruited into the study. Mean age at diagnosis was 5.97 years, and time of follow-up was 4.6 years. Etiology was idiopathic in 166 (45.5%), cryptogenic in 106 (29.0%), and symptomatic in 93 (25.5%). Focal seizures were seen in 52.9% of the patients, generalized epilepsy in 43.5%, and 3.6% were not determined. In infants, West syndrome (34.1%) and focal symptomatic seizures (24.4%) were the most prevalent syndromes. In early childhood, the main syndromes were cryptogenic focal epilepsies (17.7%) and Doose syndrome (12.8%). In school-aged children, benign epilepsies (27.3%) and absences (24.5%) were prevalent. In adolescents, cryptogenic focal epilepsies (26.6%) and benign epilepsies (23.4%).

Levetiracetam is a new antiepileptic drug whose efficacy and tolerability are already well known in adults. Few studies are available in children. This review, based on the international literature, aims to identify and make known the possible indications for levetiracetam in childhood. Most studies suggest that levetiracetam is effective against partial and generalized epilepsy. In resistant partial epilepsy, the percentage of responders reaches 64%, with 8 to 23% seizure free. Levetiracetam is used to treat symptomatic and idiopathic epilepsies. The drug has also proven effective against photosensitivity and epileptic and nonepileptic myoclonus. The most frequent side effects involve the behavioral sphere and manifest mostly in patients with a history of behavioral problems. In some patients, levetiracetam increases the number of seizures, but this adverse reaction can be partially avoided with slow titration. Doses for children should be 130 to 140% of those advised for adults. Levetiracetam seems to have a broad spectrum of action and is, on the whole, well tolerated. Its efficacy against generalized epilepsy is particularly promising in childhood. ( J Child Neurol 2005;20:87—93).

Transcranial magnetic stimulation (TMS) seems an attractive tool for the study of seizure disorders. It is simple to perform, relatively inexpensive, and generally safe, with the potential to provide noninvasive clinical measurements of neuronal excitability. Applications in patients with epilepsy include investigation of underlying cortical excitability and determination of the effects of antiepileptic drugs (AEDs); preoperative localization of epileptic foci; and functional mapping. Several review articles have been published on the use of TMS for epilepsy (1, 2, 3, 4, 5). Most intriguingly, TMS could become a new seizure treatment modality. The parameters measured by TMS include motor threshold, which is the minimal threshold for motor response in target muscle and motor evoked potential (MEP) amplitude, both measured using single pulses (see Table 1). The cortical silent period (CSP) is a lapse in electromyogram (EMG), when a TMS pulse is given during tonic voluntary muscle contraction; its duration is related to stimulus intensity. Additional parameters are measured with paired-pulse stimulation techniques. For example, intracortical inhibition (ICI), a decrease in MEP amplitude from the first to the second stimulus, is seen when a subthreshold conditioning pulse is followed by a suprathreshold pulse after a 2- to 5-millisecond delay, whereas intracortical facilitation (ICF) occurs when the pulses are 7 to 20 milliseconds apart. TABLE 1 TMS Parameters

The goal of this study was to determine whether the EEG could predict if patients with focal seizures would eventually be uncontrolled (U), more than two seizures per month, or be controlled (C), fewer than two seizures per year. Using these latter criteria, U and C patients were randomly selected from our files, 150 in each of these two groups; 804 EEGs were found in the U and 674 in the C group. Excluded were patients with generalized epilepsy and also the benign epilepsies of childhood. Age was an important factor since patients 5–18 yrs old were more often under good control (C group), and those 21–48 yrs of age were more often under poor control (U group). With rare exceptions, focal spikes and focal slow waves in every area were much more often seen in U patients than C patients. No spikes or rare spikes appeared especially in the controlled patients, and many or very many spikes in the uncontrolled patients, mainly on the first or second EEG. No slow waves or a mild degree of slowing was seen especially in the C patients, while greater degrees of slow wave abnormalities were noted much more often in the U patients. For conditions to identify the C group, the best predictors were no spikes or rare spikes, especially on the first or second EEG, properly identifying two-thirds of the C patients and misidentifying only one-fourth of the U group. To identify the U patients on any EEG, many or very many spikes at any location or frontal spikes correctly designated a U patient in 84%, but incorrectly predicted a C patient as uncontrolled in 29%. For the first or second EEG, these values were 61% and 21%. Thus, the EEG, especially by its first or second record, can predict well the probable future of the uncontrolled patient, so that extraordinary means may be instituted early to avoid a deteriorating condition. When complete EEGs are done with sleep records and the results are quantified, reasonable prediction of eventual outcome can usually occur that is much more timely than waiting over 9 yrs, using only clinical data.

Cognitive impairment is frequently observed in children with epilepsy. We aimed at addressing to what extent cognitive function is affected by paroxysmal epileptiform activity with or without clinical seizures or by clinical features characteristic of the epilepsy syndrome. To this purpose, combined electroencephalographic (EEG) recording and cognitive testing (IQ and reaction times) were performed in 28 children. Frequent epileptiform EEG discharges significantly reduced reaction time, as did the occurrence of seizures during cognitive testing. Syndrome-related factors tended to affect cognitive functions as well: children with generalized epilepsy and high average seizure frequency obtained lower scores. Linear regression analysis showed that stable aspects of cognitive function, as reflected in intelligence level, are most closely related to the severity of the epilepsy syndrome (average seizure frequency), whereas transient aspects of cognitive function, such as reaction times, are related to the occurrence of epileptiform EEG discharges. This suggests that seizures have a direct effect on transient cognitive aspects, which can accumulate and result in effects on intelligence level. ( J Child Neurol 2003;18:407—412).

Objective: To review the literature on self-induced epileptic seizures and apply psychiatric knowledge to define possible causes and treatment recommendations. Methods: A review of MEDLINE literature on self-induced epileptic seizures was conducted, followed by cross-referencing with the relevant neurologic, psychiatric and paediatric books and journals. Results: The reported prevalence of self-induction varies depending on the setting. In most instances, self-inducers are people affected by photosensitive primary generalized epilepsy, in whom self-induction is by intermittent photic stimulation or, more rarely, pattern stimulation or eye closure. Self-induced seizures are most commonly absences with spike-wave, though eyelid myoclonia and generalized myoclonic jerks occur. Earlier studies indicate that the majority of self-inducers were of subnormal intelligence but more recent ones indicate that as a group they could not be considered mentally retarded. Monitoring in a well-lit environment is indicated in any therapy-resistant photosensitive patient to determine whether or not selfinduction occurs. Self-induced epilepsy is notoriously resistant to therapy and reasons for this resistance are discussed. An explanatory model for the initiation and maintenance of selfinduction behaviour is also included. Conclusions: It is difficult to determine from published papers just what level of clinical difficulty self-induction of seizures actually posed to the patients and clinicians. In some cases there is contradictory evidence as to the degree of willfulness or self-induction. Self-induced epileptic seizures may be an important aspect of poor seizure control in a subgroup of epilepsy sufferers. These seizures might be modifiable by psychiatric intervention or behavioural modification.

There is no doubt that the frontal lobe plays a major role in the 3/sec spike-wave absence seizure. It is pointed out initially that the controversies of cortical vs. thalamic origin of the spike-waves and the associated absence can be laid at rest as far as human absence seizures and human primary generalized epilepsy (PGE) are concerned: their origin is cortical with maximal frontal lobe involvement. Experimentally-induced spike-wave bursts or spontaneous spike-waves in animals pertain to other forms of epileptic seizure disorder. The frontal maximum of the 3/sec spike-wave pattern indeed indicates maximal frontal lobe involvement including both prefrontal and frontomotor portions. The absence as such is presumed to be a suspension of the working memory--an eminently frontal lobe function. This explains the immediate restoration of ictally-impaired neurocognitive functions right at the termination of the seizures. This concept can be applied not only to the classical absence occurring in PGE but also to the rare cases of secondary bilateral synchrony with a primary frontal epileptogenic focus leading to true (though very slightly different) absences.

Despite the high incidence of epilepsy in very young children, the availability of approved antiepileptic drugs for this population is limited. This study assessed the efficacy and tolerability of levetiracetam in children younger than 2 years of age with various types of epilepsy. A single-center, retrospective chart review of 28 patients ranging in age from 2 weeks to 22 months treated with levetiracetam over a 2.5-year period was conducted. The mean dosage of levetiracetam was 39 mg/kg per day, and the mean duration of treatment was 6.3 months. The majority of patients (54%) were also taking 1 or 2 other antiepileptic drugs. A reduction in seizure frequency was found in 54%, with 14% achieving seizure freedom. Eight patients showed no response to levetiracetam treatment. Efficacy was highest among patients with generalized epilepsy. Adverse effects occurred in 2 patients and were behavioral in nature. Levetiracetam treatment was safe and effective in this group of very young patients with various types of epilepsy.

Impaired Regulation of Thalamic Pacemaker Channels Through an Imbalance of Subunit Expression in Absence Epilepsy Budde T, Caputi L, Kanyshkova T, Staak R, Abrahamczik C, Munsch T, Pape HC J Neurosci 2005;25(43):9871–9882 The role of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channel isoforms and hyperpolarization-activated cation current ( Ih) for seizure-related burst firing in thalamocortical (TC) neurons was investigated in a rat genetic model of absence epilepsy [Wistar Albino Glaxo rats, bred in Rijswijk (WAG/Rij)]. Burst discharges in TC neurons locked to seizure activity in vivo were prolonged during blockade of Ih by Cs+ and ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride). In vitro analyses revealed a hyperpolarizing shift of half-maximal Ih activation ( Vh) in WAG/Rij ( Vh = −93.2 mV) compared with nonepileptic controls [August × Copenhagen-Irish (ACI) ( Vh = −88.0 mV)]. This effect is explained by a shift of the responsiveness of Ih to cAMP toward higher concentrations in TC neurons from WAG/Rij, as revealed by application of 8-bromo-cAMP and the phosphodiesterase inhibitor IBMX. During blockade of adenylyl cyclase activity, Ih activation was similar in the two strains, whereas the difference in cAMP responsiveness persisted, thereby voting against different ambient cAMP levels between strains. Increasing the intracellular cAMP level and shifting Ih activation led to a change from burst to tonic firing mode in WAG/Rij but not in ACI rats. Furthermore, HCN1 expression was significantly increased on mRNA and protein levels, with no changes in HCN2–4 expression. In conclusion, there is an increase in HCN1 expression in the epileptic thalamus, associated with a decrease in cAMP responsiveness of Ih in TC neurons and resulting impairment to control the shift from burst to tonic firing, which, in turn, will prolong burst activity after recruitment of Ih during absence seizures.

Lennox-Gastaut syndrome, a combination of various generalized seizures including atypical absences and tonic seizures with generalized slow spike waves and mental deterioration, is often difficult to distinguish from a subgroup of myoclonic-astatic epilepsy, other generalized epilepsy syndromes, and various symptomatic generalized epilepsies. Conventional antiepileptic medication is poorly effective in this condition, particularly because various types of seizures respond differently to each given drug. Lamotrigine is effective in the various types of generalized seizures and efficacy has been demonstrated in Lennox-Gastaut syndrome. Given the potential of major mental deterioration within a matter of months in this condition, and the need of slow dose escalation in order to prevent skin rash, lamotrigine should be administered as soon as the diagnosis of Lennox-Gastaut syndrome is suspected. In addition, there is growing evidence that lamotrigine is also most useful in the subgroup of myoclonic-astatic epilepsy beginning in childhood, and that these patients should benefit from the drug like those affected by Lennox-Gastaut syndrome, as soon as the diagnosis is suspected. However, this drug may worsen other cases of myoclonic-astatic epilepsy beginning in infancy. These clinical observations add to the evidence for the need of clear diagnostic work-up before appropriate drug therapy is decided in pediatric epilepsy. (J Child Neurol 1997;12(Suppl 1):S23-S28).

Epilepsy in Friedreich's ataxia is rare. We describe a 9-year-old boy with Friedreich's ataxia who had onset of symptoms in the second year of life and developed a generalized epilepsy at age 5 years. On cerebral magnetic resonance imaging, he has a subependymal gray-matter heterotopia. We suggest that his gray-matter heterotopia might be related to his diagnosis of Friedreich's ataxia and that his early onset of symptoms might be related to the length of his guanine - adenine - Adenine (GAA) triplet repeat expansion. ( J Child Neurol 2005;20:248—250).

Primary Generalized Epilepsy (PGE) has been more hotly debated over the past decades than other forms of epileptic seizure disorder. The sudden synchronous appearance of bilateral spikes and spike-waves (mainly with myoclonus resp. absence) used to perplex the earliest generation of electroencephalographers, and the enigmatic genesis of these discharges (and seizures) has not ceased to fascinate the investigators of this phenomenon. A "centrencephalic" concept with paroxysmal discharges arising from thalamic structures and "projecting" to the cortex was championed for many years and eventually laid aside. More recently, the role of the thalamic level has been re-emphasized, mainly on the basis of experimental work. In this article, the bulk of experimental work is critically reviewed: the simian model (Papio papio), the feline, and the rodent models (Wistar rat, tottering mouse). Stress is being laid on fundamental differences between all of these models and human PGE. EEG evidence indicates a superior frontal origin of bilateral-synchronous spikes and spike-waves; depth EEG recordings in patients have failed to demonstrate primary thalamic spike generation. The heart of the matter in PGE appears to be the mechanism underlying paroxysmal discharges; above all the role of arousal. It is not awakening from sleep but the ensuing period that is critical in its epileptogenic thrust caused by alternating periods of return to drowsiness and arousing stimuli. This biphasic process gradually escalates EEG bursts to myoclonus (or absences) and possibly to a generalized tonic-clonic convulsion. Most conducive to this crescendo is the state of tiredness following a night of poor sleep. Bilateral synchrony is not precise and small time differences exist. The line between primary and secondary bilateral synchrony (with a primary cortical focus) can become blurred. Genetic predisposition to generalized paroxysms must always be considered, even in the face of a primary focus with secondary bilateral synchrony. Photosensitivity is a second paroxysm-inducing mechanism in PGE; it is much less common than the abnormal arousal ("dyshormia"); both mechanisms can be present in the same patient. Therapy and prevention of seizures in PGE are finally discussed. The concept of abnormal arousal mechanisms can be put into practice in order to prevent seizures: avoidance of sleepless nights, not always an easy task in adolescents and young adults.

To evaluate the cognitive function of epileptic children, we examined P300 in 50 patients, 32 with idiopathic generalized epilepsy (IGE) and 18 with temporal lobe epilepsy (TLE), and 39 normal children. There were significant negative correlations between age and P300 latencies at Pz and Cz in normal controls. For data analysis, we used the age-corrected latency, which was calculated as the interval between the actual and predicted P300 latencies. The predicted latency was calculated with the regression equation as the relationship between P300 latency and age in normal controls. The age-corrected P300 latencies recorded from Pz and Cz were significantly longer in patients with IGE (41.5 +/- 13.1, 42.0 +/- 12.5) than in control subjects (0 +/- 7.5, 0 +/- 7.9). There were no significant differences in age-corrected P300 latencies between patients with TLE (21.2 +/- 17.6, 31.5 +/- 17.0) and controls, or IGE and TLE. Recently, it was considered that the mesencephalic reticular formation and thalamus may play major roles in the genesis of generalized epilepsy, so we speculate that dysfunction of these systems may contribute to the prolongation of P300 in children with idiopathic generalized epilepsy.

OBJECTIVE: To report a case of seizures in a patient who started receiving olanzapine, and to review seizure risk associated with antipsychotic use. CASE SUMMARY: A 31-year-old African-American woman with multiple psychiatric and medical disorders, including generalized seizure disorder, experienced seizure activity when switched from haloperidol to olanzapine. Olanzapine was discontinued, haloperidol was quickly titrated to the previous dose, and the patient was started on oral phenytoin with no further seizure activity noted. The patient remained seizure free and phenytoin was discontinued without complications. DISCUSSION: Determining causality in this case is complicated by the number of confounding factors that may have contributed to the occurrence of seizures in this patient. These factors include: (1) diagnosis of generalized seizure disorder, (2) diagnosis of organic mental disorder, (3) concurrent pharmacotherapy with medications implicated in lowering the seizure threshold, and (4) abrupt change in pharmacotherapy. The likelihood that a significant drug interaction precipitated seizure activity is doubtful. CONCLUSIONS: Considering all factors related to causality, the likelihood that olanzapine was responsible for precipitating seizure activity in this patient was judged possible. Although premarketing studies have indicated that olanzapine may be associated with minimal seizure liability, this case serves as a reminder that postmarketing surveillance of newly released medications is essential.

The effects of sleep and sleep deprivation on epilepsy are well known, but the effects of seizures and antiepileptic drugs (AEDs) on sleep have been less well studied. We recorded nocturnal sleep in 17 patients receiving antiepileptic monotherapy with ambulatory cassette EEG devices. Twelve patients had complex partial seizures and five had tonic-clonic convulsions. Two patients' seizures were largely nocturnal, and no seizures occurred during sleep recording. Five patients each were taking phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA), and two were taking clonazepam (CZP), all with therapeutic serum levels and no toxic symptoms. Total sleep time was reduced, wakefulness increased, and sleep latency prolonged in partial seizures as compared with generalized epilepsy. REM sleep was reduced and its latency decreased in partial seizure patients. Both groups had decreased slow wave sleep; that of partial seizure patients was decreased more markedly. PHT increased sleep latency and decreased sleep time, and CBZ increased awakening and diminished slow wave and REM sleep. Patients taking VPA had slight reduction in slow wave sleep; those taking CPZ had decreased sleep and REM latencies. Epilepsy may affect nocturnal sleep, and the effects of partial and generalized seizure disorders may be different. AEDs may also have differential effects on nighttime sleep. These may prove important in the long-term management of epileptic patients.

Very little data are available on the usefulness of oxcarbazepine in young children with epilepsy. From January 1991 through October 1994, we treated 53 children under age 7 years with oxcarbazepine. The mean follow-up with oxcarbazepine treat ment was 13 months. Etiology was symptomatic in 39, cryptogenic in 12, and idiopathic in 2 children. Forty-three children had previously been intractable to one or more antiepileptic drugs (including carbamazepine in 30 patients) and two had carbamazepine hypersensitivity. The age at onset of oxcarbazepine therapy ranged from 0.6 to 6.9 years (mean, 3.9 yr). The mean maximum oxcarbazepine dose was 50 mg/kg/day (range, 21-86 mg/kg/day). Of the children with localization-related epilepsy, 12 of 44 (27%) became seizure free and an additional 16 of 44 (36%) had an at least 50% reduction of seizures. Five of nine children with generalized epilepsy also had some benefit but none became seizure free. In the 33 children with at least 50% seizure reduction, the mean effective dose and trough serum level of the active metabolite monohydroxycarbazepine were 47 mg/kg/day (range, 21-75 mg/kg/day) and 91 μmol/L (range, 42-130 μmol/L), respectively. Efficacy was transient in 4 children; side effects were observed in 17 children (32%); in 9 (17%) of whom, they led to dose reduction or discontinuation. Oxcarbazepine appears to be an effective and well-tolerated drug for localization-related early childhood epilepsy. Young children need a higher dose per body weight than adults. (J Child Neurol 1997;12:496-498).

A 52-year-old African American female presented with severe left thigh pain of unknown etiology. She had a past medical history of generalized seizure disorder treated with phenytoin for 7 years without incident. During admission a nurse witnessed a seizure, and consequently loading and maintenance doses of phenytoin were administered to obtain a therapeutic serum concentration. The patient had a history of noncompliance with multiple subtherapeutic phenytoin levels. Subsequently, unifocal blue discolored spots appeared, progressing to a bullous component that was positive for skin sloughing. Drug-induced fixed drug eruption was diagnosed and attributed to phenytoin. Clinicians should be cognizant of drug-induced fixed drug eruption in patients just initiated and those receiving long-term treatment with phenytoin. The administration rate of phenytoin may be associated with the development of fixed drug eruption.

Phenobarbital, the oldest of the currently available antiepileptic drugs, has lost its popularity in this era of multiple new drugs and is seldom used after infancy in developed countries. We report a group of patients with generalized epilepsy in whom phenobarbital proved to be the drug of choice. Phenobarbital monotherapy was given to 20 patients with idiopathic generalized epilepsy beginning in childhood but persisting into adulthood. All the patients have normal intelligence and neurologic status. The electroencephalogram has either been normal or showed generalized spike-wave discharges. All patients' seizures are fully controlled on once-a-day low-dose phenobarbital with no side effects. Attempts to discontinue the medication have led to recurrence of seizures. We believe that in patients with mild generalized tonic-clonic seizures phenobarbital could still be the drug of choice since it is cheap, safe, convenient, and effective. ( J Child Neurol 1999;14:820-821).

The antiepileptic effect of vigabatrin in adults has been demonstrated in a number of controlled studies. In children, the effect of vigabatrin has been investigated only to a limited extent. In order to assess the long-term effect and safety of vigabatrin in patients with severe epilepsy, an open, add-on, dose-ranging study was initiated. To date, 27 children with partial epilepsy, two with generalized epilepsy, two with Lennox-Gastaut syndrome, and one with nonclassifiable epilepsy have been enrolled in the trial. Fifty-four percent of patients have experienced a greater than 50% reduction in seizure frequency, and four patients have become seizure free. A significant reduction in seizures was noted across the patient population, although patients who were recorded as seizure free at 3 and 6 months did suffer some recurrence of seizures. However, when seizures recurred, they did so at much lower frequency than recorded at the start of the study. Thirteen patients (39%) reported adverse events attributable to vigabatrin; one was immediately withdrawn from the study, and six had their vigabatrin dose reduced. No physiologic effects were noted on normal growth or clinical physical examination. (J Child Neurol 1991;6(Suppl):2S38-2S44).

Abnormal arousal responses paired with paroxysmal discharges and photosensitivity are the principal mechanisms in the precipitation of seizures in primary generalized epilepsy. The abnormal arousal responses show a consistent maximum over the frontal midline region. An exception from this rule was found in two children with primary generalized epilepsy (petit mal absences, one also with grand mal) with a strongly positive family history. In these patients, the generalized-synchronous bursts showed a maximum over the vertex (Cz electrode). Both of these children also had single spikes over the Rolandic region. A relationship between primary generalized and benign Rolandic epilepsy is demonstrated. Both forms of seizure disorder are based on dysfunction (hyperexcitability) rather than on a structural epileptogenic lesion. A dichotomy of dysfunctional and structural epilepsies is presented but gray zones of overlap indubitably exist. The limitations of the dichotomy concept are pointed out.