Successful antiepileptic drug withdrawal in infants with epilepsy and cytomegalovirus neuroinfection: Longitudinal study

Purpose: A prospective study estimating antiepileptic and antiviral regimens administered to infants with symptomatic epilepsy and human cytomegalovirus (HCMV) neuroinfection followed for at least 4 years. Methods: Thirty‐two infants (19 female, 13 male) with epileptic seizures and HCMV neuroinfection diagnosed during the first year of life. Detection of HCMV DNA by qualitative polymerase chain reaction (PCR) method in cerebrospinal fluid (CSF), blood leukocytes, and urine confirmed the diagnosis. Infants were treated with intravenous ganciclovir (GCV) and different antiepileptic drugs. All had multiple electroencephalographic and neuroimaging examinations. Outcome of seizures was assessed using Engel classification system in the child’s fourth year of life. Results: Cessation of seizures was achieved in 19 infants (59.4%). In 11 children (34.4%) it was possible to withdraw administration of AEDs after 30–36 months. No infantile spasms, generalized tonic–clonic seizures, or polymorphic seizures were observed. They remained seizure‐free for 1–6 years without relapse and their psychomotor development was normal. Four patients with intractable epilepsy (class V) had the longest GCV treatment (median 8 weeks). GCV treatment was implemented at the time or within 1 month after the onset of epileptic seizures in 10 of 11 infants withdrawn from AEDs. Conclusion: Early introduction of antiepileptic and antiviral GCV regimens in epilepsy and CMV neuroinfection may result in discontinuation of antiepileptic treatment and normal psychomotor development in infants.     

Clinical Electroencephalographic Biomarker for Impending Epilepsy in Asymptomatic Tuberous Sclerosis Complex Infants

BackgroundWe assessed the clinical utility of routine electroencephalography (EEG) in the prediction of epilepsy onset in asymptomatic infants with tuberous sclerosis complex.MethodsThis multicenter prospective observational study recruited infants younger than 7 months, seizure-free and on no antiepileptic drugs at enrollment, who all underwent serial physical examinations and video EEGs throughout the study. Parental education on seizure recognition was completed at the time of initial enrollment. Once seizure onset occurred, standard of care was applied, and subjects were followed up until 24 months.ResultsForty patients were enrolled, 28 older than 12 months with completed EEG evaluation at the time of this interim analysis. Of those, 19 (67.8%) developed seizures. Epileptic spasms occurred in 10 (52.6%), focal seizures in five (26.3%), generalized tonic-clonic seizure in one (5.3%), and a combination of epileptic spasms and focal seizures in three (15.7%). Fourteen infants (73.6%) had the first emergence of epileptiform abnormalities on EEG at an average age 4.2 months, preceding seizure onset by a median of 1.9 months. Hypsarrhythmia or modified hypsarrhythmia was not found in any infant before onset of epileptic spasms. All children with epileptiform discharges subsequently developed epilepsy (100% positive predictive value), and the negative predictive value for not developing epilepsy after a normal EEG was 64%.ConclusionsSerial routine EEGs in infants with tuberous sclerosis complex is a feasible strategy to identify individuals at high risk for epilepsy. The most frequent clinical presentation was epileptic spasms followed by focal seizures, and then a combination of both seizure types.     

Epileptic spasms without hypsarrhythmia showing astatic seizures in clusters

It is difficult to differentiate astatic seizures among atonic, myoclonic and tonic seizures without the help of ictal polygraphic recordings. We described a girl with epilepsy presenting periodic astasia caused by epileptic spasms. Her seizures had occurred in clusters since 1-year and 7-month of age. Her interictal electroencephalogram (EEG) showed intermittent diffuse (poly) spike (s) and wave discharges, without a trace of hypsarrhythmia. She had a diagnosis of epilepsy with myoclonic-astatic seizures at a previous hospital, and her seizures had been resistant to multiple antiepileptic agents. After she was referred to our hospital, the ictal video-EEG recordings were made before and after ACTH administration, which revealed that her astatic seizures were epileptic spasms with presumed cortical origin. We should carefully evaluate the astatic seizures during early childhood which may be an atypical presentation of epileptic spasms.     

Clinical seizure semiology is subtle and identification of seizures by parents is unreliable in infants with tuberous sclerosis complex

Objective

The objectives of this study were to assess the accuracy of parental seizure detection in infants with antenatally diagnosed tuberous sclerosis complex (TSC), and to document the total seizure burden (clinical and subclinical) in those patients who met criteria for prolonged electroencephalography (EEG) recording.

Methods

Consecutive infants at a single institution with antenatally diagnosed TSC who met criteria for prolonged video-EEG (vEEG) were recruited to this study. The vEEG data were reviewed and when a seizure was identified on EEG, the video and audio recording was assessed for evidence of clinical seizure and, if present, whether there was evidence of parent seizure identification.

Results

Nine infants were enrolled, for whom 674 focal seizures were identified in eight of nine patients across 24 prolonged vEEG recordings, with vEEG total duration of 634 h 49 min (average seizure frequency of 1 focal seizure/h). Only 220 of 674 (32.6%) were clinical seizures, 395 of 674 (58.6%) were subclinical seizures, and 59 of 674 seizures could not be classified. Only 63 of 220 clinical seizures (28.6%) were identified by parents, with 157 of 220 (71.4%) not identified. Thirty clusters of epileptic spasms were detected in one patient. At least one clinical epileptic spasm occurred in 2 of 30 clusters (6.7%), 24 of 30 clusters of epileptic spasms (80%) were electrographic only, and classification was uncertain for 4 of 30 clusters (13.3%). No clinical epileptic spasms were detected by parents. Clinical seizure frequency was significantly underestimated by parents for all patients.

Significance

This study demonstrates that in infants with TSC who met criteria for prolonged vEEG, (1) parents significantly under recognize total clinical seizure count, (2) parents fail to identify epileptic spasms, and (3) seizure frequency is high. This highlights that epilepsy treatment decisions should not be based solely on parental clinical seizure identification. Prolonged vEEG monitoring may have an important role in the routine epilepsy care of infants with TSC, as demonstrating undetected high clinical seizure frequency may allow improved epilepsy management decisions.     

Treatment guidelines for adult epilepsy]

We reviewed the treatment strategies and choices of drugs for adult patients with epilepsy. As evidence from controlled studies for the older drugs is scarcely available from the literature, we added a clinical study performed in our hospital and an expert consensus study. Published randomized clinical studies revealed carbamazepine (CBZ) to be the treatment of choice, but provided little evidence for the differences in efficacy between phenytoin (PHT), valproate (VPA), phenobarbital (PB) and zonisamide (ZNS). The clinical study in our patients with intractable localization-related epilepsy indicated the superior efficacy of CBZ and PHT over VPA or ZNS. Sixty-nine experts converged on the opinion that monotherapy should be started with VPA for seizures of both idiopathic and symptomatic generalized epilepsy, and with CBZ for seizures of localization-related epilepsy. When the trials with 2-3 monotherapy failed, surgery should be considered for localization-related epilepsy. We proposed practical guidelines for treatment of patients with adult epilepsy, including rehabilitation and care for improvement of quality of life.     

Evidence-based Treatment of Idiopathic Generalized Epilepsies with Older Antiepileptic Drugs

Summary:  Older antiepileptic drugs continue to play a major role in the treatment of the idiopathic generalized epilepsies. Comparative studies of ethosuximide and valproate have demonstrated equivalence in the treatment of childhood absence epilepsy. Valproate can be regarded as the recommended first-line treatment for juvenile myoclonic epilepsy based on case series reports. Studies in patients with generalized tonic-clonic seizures have not separated out idiopathic from secondary generalized events. Treatment for the other idiopathic generalized epilepsy syndromes lacks evidence other than a few case reports and diverse expert opinion. Further randomized controlled trials of older antiepileptic drugs are recommended to solidify the evidence-based treatment of the idiopathic generalized epilepsies.     

Treatment of pediatric epilepsy: European expert opinion, 2007.

BACKGROUND: Childhood epilepsies are a heterogeneous group of conditions that differ in diagnostic criteria and management and have dramatically different outcomes. Despite increasing data on treatment of epilepsy, research findings on childhood epilepsy are more limited and many clinical questions remain unanswered, so that clinicians must often rely on clinical judgment. In such clinical situations, expert opinion can be especially helpful. METHODS: A survey on pediatric epilepsy and seizures (33 questions and approximately 650 treatment options) was sent to 57 European physicians specializing in pediatric epilepsy, 42 (74%) of whom completed it. In some questions, the experts were asked to recommend overall treatment approaches for specific syndromes (the order in which they would use certain strategies). Most of the questions asked the experts to rate options using a modified version of the RAND 9-point scale for medical appropriateness. Consensus was defined as a non-random distribution of scores by chi-square test, with ratings used to assign a categorical rank (first line/usually appropriate, second line/equivocal, and third line/usually not appropriate) to each option. RESULTS: Valproate was treatment of choice for symptomatic myoclonic and generalized tonic-clonic seizures. For initial monotherapy for complex partial seizures, carbamazepine and oxcarbazepine were treatments of choice, with valproate also first line. As initial therapy for infantile spasms caused by tuberous sclerosis, viagabatrin was treatment of choice. As initial therapy for infantile spasms that are symptomatic in etiology, vigabatrin was also treatment of choice, with adrenocorticotropic hormone (ACTH) and prednisone other first-line options. As initial therapy for Lennox-Gastaut syndrome, valproate was treatment of choice. For acute treatment of a prolonged febrile seizure or cluster of seizures, rectal diazepam was treatment of choice. Valproate was treatment of choice as preventive therapy for febrile seizures. For benign childhood epilepsy with centro-temporal spikes, valproate was treatment of choice. For childhood and juvenile absence epilepsy, valproate was treatment of choice, with lamotrigine another first-line option (ethosuximide was another first-line option for childhood absence epilepsy). For juvenile myoclonic epilepsy in adolescent males, valproate was treatment of choice, with lamotrigine another first-line option; for juvenile myoclonic epilepsy in adolescent females, lamotrigine was treatment of choice, with valproate another firstline option. As initial therapy for neonatal status epilepticus, intravenous (IV) phenobarbital was treatment of choice. As initial therapy for all types of pediatric status epilepticus, IV diazepam was treatment of choice. For generalized tonic-clonic status epilepticus, rectal diazepam and IV lorazepam were also treatments of choice; for complex partial status epilepticus, IV lorazepam was another first-line option. CONCLUSION: The expert panel reached consensus on many treatment options. Within the limits of expert opinion and with the understanding that new research data may take precedence, the experts' recommendations provide helpful guidance in situations where the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings.     

Selection of drugs for the treatment of epilepsy

Antiepileptic drug selection is based on efficacy for specific seizure types and epileptic syndromes. For idiopathic generalized epilepsies with absence, tonic-clonic, and myoclonic seizures, the drug of choice is valproate. Secondary generalized epilepsies with tonic, atonic, and other seizure types are difficult to treat with any single drug or combination of drugs. The drugs of choice for absence seizures are ethosuximide and valproate. For control of tonic-clonic seizures, any of the other major antiepileptic drugs can be effective. If valproate cannot be used, carbamazepine, phenobarbital, phenytoin, or primidone is effective, but ethosuximide or a benzodiazepine needs to be added to control associated absence or myoclonic seizures. The drugs of first choice for partial epilepsies with partial and secondarily tonic-clonic seizures are carbamazepine and phenytoin. Increasing evidence suggests that valproate may be a third alternative. Phenobarbital and primidone are second choice selections because of side effects. A combination of two of these five major antiepileptic drugs may be necessary for inadequately controlled patients. Other epilepsy syndromes such as neonatal and infantile epilepsies, febrile epilepsy, and alcoholic epilepsy require specific drug treatment. For all these seizure types and epilepsy syndromes, treatment ultimately must be selected to provide maximal efficacy and minimal adverse effect for each individual patient.     

Cerebrospinal Fluid γ-Aminobutyric Acid Levels in Children with Different Types of Epilepsy: Effect of Anticonvulsant Treatment

The mean gamma-aminobutyric acid (GABA) level in lumbar CSF of 31 children with epilepsy was not significantly different from that of 41 age-matched controls. However, when the epileptic children were subdivided into untreated patients and patients treated with antiepileptic drugs, the medication-free subgroup had a significantly lower mean CSF GABA level than nonepileptic children. Patients controlled by anticonvulsant therapy had significantly higher CSF GABA levels than untreated epileptic patients. A more detailed analysis of the children taking antiepileptic medication indicated that the only drug that significantly increased GABA in CSF was valproic acid. Analysis of CSF data with respect to the seizure type of the patients showed that, compared with controls, significantly reduced average GABA levels were present in children with infantile spasms (mostly untreated) and unmedicated generalized tonic-clonic seizures, whereas treated children with generalized tonic-clonic seizures and patients with partial epilepsy (mostly treated) did not significantly differ from controls. The data provide further evidence that impairment of the central GABA system may be involved in human epilepsy.     

Investigational Antiepileptic Drugs for the Treatment of Childhood Seizure Disorders: A Review of Efficacy and Safety

Summary: Pediatric epileptology is very different from adult epileptology. Although some epileptic disorders occur in both children and adults (e.g., localization-related epilepsy with complex partial seizures and primary generalized epilepsy with tonic-clonic seizures), other disorders can be called the catastrophic epilepsies of childhood (e.g., infantile spasms and the Lennox-Gastaut syndrome). They occur, or at least begin, exclusively in childhood and are often associated with mental retardation. Many of these pediatric disorders are notoriously unresponsive to currently available antiepileptic drugs (AEDs). Although there are undoubtedly many reasons for this, one possible explanation is that the methods used to screen potential AEDs use animal models of adult epilepsy. No screening program uses an animal model of seizures that begin during development and lead to functional decline.     

Prognosis of seizures occurring in the first year

To determine whether predictors of neurodevelopmental outcome and the course of epilepsy can be identified in infants 1-12 months of age presenting with their first afebrile seizure, we collected demographic data, seizure details (type, frequency, duration, etiology, and treatment), developmental status, neurologic findings at presentation and follow-up, and electroencephalographic (EEG), neuroimaging, metabolic, hematologic, and chemistry test results by chart review, parental interview, and neurologic examination in 40/41 subjects (98%) presenting to our institution between January 1994 and December 1998. The mean duration of follow-up from onset of seizures was 29 months (S.D. = 17; range = 1-64). Predictors of developmental and neurologic abnormalities at follow-up included developmental delay and abnormal neurologic examination at presentation, infantile spasms, lack of response to antiepileptic drugs (AEDs), valproate use, and abnormal EEG or neuroimaging results. Predictors against seizure control and epilepsy remission and for the development of problematic seizures at follow-up included valproate use and lack of response to AEDs. Poor neurodevelopmental outcome of children with new-onset afebrile seizures in the first 1-12 months of age can be accurately predicted at diagnosis with the aid of EEG and neuroimaging studies. The course of epilepsy is more difficult to predict, but failure to respond to the first AED is worrisome.     

Treatment of seizures in the neonate: Guidelines and consensus-based recommendations—Special report from the ILAE Task Force on Neonatal Seizures

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic–ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.     

The Role of Perinatal Brain Injury in the Genesis of Childhood Epilepsy

In order to elucidate the significance of perinatal brain damage in the etiology of epilepsy, 139 full-term neonates considered to have suffered a severe degree of perinatal hypoxia were examined neurologically and electroencephalographically for two-nine years. Thirty-eight (27.3%) of them developed epileptic seizures during the follow-up period. Sixteen infants developed infantile spasms at ages two-13 months, while 10 manifested generalized motor seizures mainly at one-four years. They all had neonatal background EEGs suggesting a severe degree of brain damage, although the infants with infantile spasms and myoclonic seizures showed more abnormal neonatal EEGs than those with other types of fits.
The combination of multiple factors, mainly exogenous and constitutional, is necessary for the development of epileptic seizures, especially in patients with a lesser degree of brain damage.     

Symptomatology of Epileptic Seizures in the First Three Years of Life

PURPOSE: Few data are available concerning symptomatology of epileptic seizures in infants. METHODS: We reviewed 296 videotaped seizures from 76 patients aged 1-35 months (mean, 15.1 months) who underwent video-EEG monitoring at our institution from 1988 to 1998. Seizure symptomatology was first classified based on observable behavioral and motor manifestations and then correlated with ictal EEG. RESULTS: Four seizure types accounted for 81% of all seizures seen in this group: epileptic spasms (24%), clonic seizures (20%), tonic seizures (17%), and hypomotor seizures (20%; characterized by arrest or significant decrease of behavioral motor activity with indeterminate level of consciousness). The remaining seizures included small numbers of myoclonic, atonic, and versive seizures. All 12 focal motor seizures and all five versive seizures were associated with focal EEG seizure patterns, seen in the contralateral hemisphere in all but one patient with versive seizures. Generalized motor seizures (clinically generalized at onset) were accompanied either by focal (19 of 51; 37%) or generalized (32 of 51; 63%) EEG seizures. Hypomotor seizures also were associated with focal (14 of 20; 70%) or generalized (six of 20; 30%) EEG seizures. Four patients with generalized epileptic spasms had generalized EEG seizures in the setting of focal epilepsy based on neuroimaging, interictal EEG, and in two cases also on postresection seizure freedom. Seizure types not seen in this age group included auras, seizures with prominent automatisms (except in one case), and classic generalized tonic-clonic seizures. CONCLUSIONS: The repertoire of seizure manifestation in the first 3 years of life appears to be limited. In infants, focal motor seizures are reliably associated with focal EEG seizures in the contralateral hemisphere, whereas generalized motor and hypomotor clinical seizures may be either focal or generalized on EEG. Epileptic spasms may be seen in focal as well as generalized epilepsies. Video-EEG monitoring and neuroimaging may be critical for clarifying the focal or generalized nature of the epilepsy in infants.     

Effect of corticosteroids in a twin child with idiopathic localization-related epilepsy

Corticosteroids have been used only in the treatment of special epileptic syndromes or epileptic encephalopathies, such as infantile spasms. We report an antiepileptic effect of corticosteroids that were used for treatment of nephropathy in a monozygotic twin child with idiopathic localization-related epilepsy (I-LRE). The patient and her monozygotic twin sister exhibited repeated partial seizures at two years of age and electroencephalogram (EEG) showed focal spikes in the occipital area and, on other occasions, the centro-parietal areas. After oral antiepileptic drugs were started, the twins still exhibited occasional seizures. The patient had IgA nephropathy at four years of age and intravenous methylprednisolone and oral prednisolone were administered. Her seizures and epileptiform discharges on EEG disappeared, while her sister continued to have seizures and EEG abnormalities. When the dose of oral predonisone was reduced, the seizures relapsed and EEG again revealed focal spikes. We conclude that corticosteroids exhibit efficacy towards seizures and epileptiform discharges on EEG in patients with I-LRE without epileptic encephalopathies.     

Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability

The main principles of antiepileptic drug treatment of epilepsy in patients with intellectual disability are basically the same as for other patients with epilepsy. However, some specific issues need to be taken into account These are primarily associated with the diagnostic difficulties of epilepsy in this population. In addition, a number of other relevant issues, including the degree and location of brain lesion, the nature of the underlying disease, the higher frequency of difficult-to-treat epilepsies, the additional intellectual impairment caused by inappropriate antiepileptic medication, or by frequent and prolonged seizures, the appropriate use of monotherapy versus rational polytherapy, and the use of broad-spectrum antiepileptic drugs will be discussed in the present paper. Although the goals of treatment are to keep the patient seizure-free and alert while preventing possible mental deterioration, we have to accept compromises between these primary goals in many cases. Some people with epilepsy and intellectual disability are very vulnerable to insidious neurotoxic effects; for example, sedative effects caused by phenobarbital, or cognitive and/or cerebellar dysfunction caused by long-term phenytoin, especially together with other drugs. Because of the adverse effects of phenobarbital and phenytoin, these drugs are no longer recommended as a first-choice drugs when long-term antiepileptic medication is required. In primary generalized tonic-clonic seizures, valproate, oxcarbazepine/carbamazepine and lamotrigine are recommended in this order of preference. The corresponding recommendations are: in typical absences, valproate, ethosuximide and lamotrigine; in atypical absences, valproate and lamotrigine; in juvenile myoclonic epilepsy, valproate, lamotrigine and clobazam; in infantile spasms vigabatrin, ACTH and valproate; in Lennox-Gastaut syndrome, valproate, lamotrigine and vigabatrin; in atonic seizures, valproate and lamotrigine; in simple and complex partial seizures with or without secondary generalization, oxcarbazepine/carbamazepine, valproate/ vigabatrin and lamotrigine; and in status epilepticus lorazepam, diazepam and clonazepam together with phenytoin or fosphenytoin. In cases of poor response to the monotherapy recommended above, the following combinations may be indicated: in primary generalized tonic-clonic epilepsy, valproate and oxcarbazepine/ carbamazepine, or valproate and lamotrigine; in typical absences, valproate and lamotrigine, or valproate and ethosuximide; in juvenile myolonic epilepsy, valproate and lamotrigine, or valproate and clonazepam; and in partial epilepsies, add to the monotherapy one of the following drugs, vigabatrin, lamotrigine, gabapentin, tiagabine, topiramate, zonisamide or clobazam. So far, the order of preference of these new drugs remains undetermined. More data are needed on the efficacy and adverse effects of the new drugs based on controlled studies on patients with intellectual disability and epilepsy.     

Subsequent Epilepsy in Very-Low-Birthweight Infants: A Long-Term Follow-up Study from Birth

Summary: We studied 197 survivors of 290 very-low-birthweight (VLBW, <1,500g) infants admitted to our neonatal intensive care unit from 1977 through 1982. The children were all followed until at least age 6 years (mean 10 years 6 months). Eight children (4.1%) had epilepsy: 5 had generalized, 2 had unilateral, and 1 had partial seizures. Two (1.0%) had active and poorly controlled epilepsy. Three had a history of epileptic seizures, but none for ≥ 6 years, and 3 were no longer receiving antiepileptic drug (AED) treatment. Most (5 of 8) were severely multiply handicapped. As compared with VLBW children without epileptic seizures and neurodevelopmental abnormalities, VLBW children with epileptic seizures had a gestational age <27 weeks, a weight <1,000 g, severe perinatal complications as indicated by an Apgar score of <4 at 5 min, and the need for long-term oxygen administration.     

Therapie von Epilepsien im Kindes- und Jugendalter

Therapeutic strategies for treating epilepsy in childhood and adolescence markedly depend on the underlying electroclinical syndromes. In self-limiting epilepsies with focal seizures of genetic or unknown etiology, e.g. benign infantile seizures, rolandic epilepsy and Panayiotopoulos syndrome, a considerable number of patients may not require any pharmacological therapy but if they do, sulthiame, levetiracetam or oxcarbazepine should easily control seizures. Early application of corticosteroids should be considered in atypical forms, such as pseudo-Lennox syndrome, syndrome of continuous spike waves in sleep (CSWS) and Landau-Kleffner syndrome. Lamotrigine, slow release oxcarbazepine and levetiracetam are drugs of first choice for treating focal seizures in epilepsy of structural/metabolic or unknown causes. Various antiepileptic drugs are available in case of difficulties in controlling seizures; however, the possibility of epilepsy surgery should be evaluated early in these cases. Ethosuximide is the first line drug in childhood absence while valproate is the most effective drug in juvenile absence epilepsy and juvenile myoclonic epilepsy. Because of the lower teratogenic risk an initial trial with lamotrigine, possibly combined with levetiracetam is justified in girls. Valproate, lamotrigine and ethosuximide are the most important options in myoclonic atonic epilepsy. In addition, a ketogenic diet is a promising option. While corticosteroids and vigabatrin should be administered for infantile spasms, valproate is the basis for different combinations in the treatment of Lennox-Gastaut syndrome. Efficacy of lamotrigine, topiramate, rufinamide, clobazam and felbamate has been shown in placebo-controlled randomized trials. Vagus nerve stimulation and ketogenic diets are further options. In cases of Dravet syndrome early treatment with either bromide or valproate in combination with clobazam and stiripentol should be established. Combinations of valproate, topiramate and bromide and ketogenic can be effective. In general, the increasing number of available anticonvulsants allows an individually optimized therapeutic strategy in many cases, considering gender, age, body weight, behavior and cognition. Maintaining the best possible development should always be a major issue in the treatment of childhood epilepsy.     

Clinical characteristics and use of antiepileptic drugs among adolescents with uncomplicated epilepsy at a referral center in Novi Sad, Serbia

The study aimed to investigate the type and etiology of epileptic seizures and the use of antiepileptic drugs for the treatment of various forms of epileptic seizures among adolescents with active but uncomplicated epilepsy at a tertiary referral center in Novi Sad, Serbia. The study design was cross sectional. Data were obtained from patients and medical records. A total of 103 adolescents (39 males and 64 females) with active but uncomplicated epilepsy were included. Patients with primary generalized seizures had significantly better control of epilepsy than those with partial seizures with or without secondary generalization. A total of 80 (77.7%) adolescents had no known underlying etiology based on initial diagnosis and evaluation. All adolescents were classified into known idiopathic syndromes (54.4%), non-classifiable cryptogenic etiology (23.3%), and secondary epilepsy attributed to MRI-identified lesions (22.3%). Eighty-eight percent of adolescents were taking monotherapy and 64.8% of these were taking valproate. New antiepileptic drugs (AEDs), topiramate and lamotrigine, the only drugs available free of charge at the Serbian market, were used in 19.4% of patients. A total of 57.3% adolescents were seizure-free, 24.2% had occasional seizures, and 18.5% had seizures despite AED treatment.