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To evaluate the efficacy and tolerability of adjunctive levetiracetam in very young children (aged 1 month to <4 years) with partial-onset seizures inadequately controlled with one or two antiepileptic drugs. This multicenter, double-blind, randomized, placebo-controlled study consisted of a 48-h inpatient baseline video-EEG (electroencephalography) and a 5-day inpatient treatment period (1-day up-titration; 48-h evaluation video-EEG in the last 2 days). Children who experienced at least two partial-onset seizures during the 48-h baseline video-EEG were randomized to either levetiracetam [40 mg/kg/day (age 1 to <6 months); 50 mg/kg/day (age ≥6 months to <4 years] or placebo. Of 175 patients screened, 116 patients were randomized [60 levetiracetam; 56 placebo; intent-to-treat (ITT) population], and 111 completed the study. The responder rate in average daily partial-onset seizures frequency (48-h video-EEG monitoring; primary efficacy variable) was 43.1% for levetiracetam [modified ITT (mITT) = 58] versus 19.6% for placebo (mITT = 51; p=0.013), with odds ratio for response 3.11 [95% confidence interval (CI), 1.22–8.26]. The median percent reduction from baseline in average daily partial-onset seizure frequency was 43.6% for levetiracetam and 7.1% for placebo with a median difference between treatment groups of 39.2% (95% CI, 17.5–62.2; p < 0.001). In general, levetiracetam was well tolerated. Treatment-emergent adverse events were reported by 55.0% levetiracetam- and 44.6% placebo-treated patients (ITT population). The most frequently reported adverse events were somnolence (13.3% levetiracetam, 1.8% placebo) and irritability (11.7% levetiracetam, 0% placebo). Adjunctive levetiracetam is an efficacious and well-tolerated treatment for partial-onset seizures in infants and young children. [ABSTRACT FROM AUTHOR]

Background: Infantile spasms constitutes a severe infantile epilepsy syndrome that is difficult to treat and has a high morbidity. Hormonal therapies or vigabatrin are the most commonly used treatments. We aimed to assess whether combining the treatments would be more effective than hormonal therapy alone.Methods: In this multicentre, open-label randomised trial, 102 hospitals (Australia [three], Germany [11], New Zealand [two], Switzerland [three], and the UK [83]) enrolled infants who had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG no more than 7 days before enrolment. Participants were randomly assigned (1:1) by a secure website to receive hormonal therapy with vigabatrin or hormonal therapy alone. If parents consented, there was an additional randomisation (1:1) of type of hormonal therapy used (prednisolone or tetracosactide depot). Block randomisation was stratified for hormonal treatment and risk of developmental impairment. Parents and clinicians were not masked to therapy, but investigators assessing electro-clinical outcome were masked to treatment allocation. Minimum doses were prednisolone 10 mg four times a day or intramuscular tetracosactide depot 0·5 mg (40 IU) on alternate days with or without vigabatrin 100 mg/kg per day. The primary outcome was cessation of spasms, which was defined as no witnessed spasms on and between day 14 and day 42 from trial entry, as recorded by parents and carers in a seizure diary. Analysis was by intention to treat. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 54363174, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2006-000788-27.Findings: Between March 7, 2007, and May 22, 2014, 766 infants were screened and, of those, 377 were randomly assigned to hormonal therapy with vigabatrin (186) or hormonal therapy alone (191). All 377 infants were assessed for the primary outcome. Between days 14 and 42 inclusive no spasms were witnessed in 133 (72%) of 186 patients on hormonal therapy with vigabatrin compared with 108 (57%) of 191 patients on hormonal therapy alone (difference 15·0%, 95% CI 5·1-24·9, p=0·002). Serious adverse reactions necessitating hospitalisation occurred in 33 infants (16 on hormonal therapy alone and 17 on hormonal therapy with vigabatrin). The most common serious adverse reaction was infection occurring in five infants on hormonal therapy alone and four on hormonal therapy with vigabatrin. There were no deaths attributable to treatment.Interpretation: Hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone. The 4 week period of spasm cessation required to achieve a primary clinical response to treatment suggests that the effect seen might be sustained, but this needs to be confirmed at the 18 month follow-up.Funding: The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, the BRONNER-BENDUNG Stifung/Gernsbach, and University Children's Hospital Zurich. [ABSTRACT FROM AUTHOR]

Objectives This report aims to define treatment goals, to summarize the level of the evidence of different treatment options for infantile spasms (IS), both in terms of efficacy and adverse effect, and to give recommendations for the management of IS. Methods The Cochrane and Medline (1966-July 2014) databases were searched. Literature known to the guideline working group and identified through citations was also considered. The results of previously published guidelines were taken into account in our analysis. Rating the level of evidence followed the Scottish Intercollegiate Guidelines Network. Recommendations If IS are suspected, electroencephalogram (EEG) should be performed within a few days and, if confirmed, treatment should be initiated immediately. Response to first-line treatments should be evaluated clinically and electroencephalographically after 14 days. Adrenocorticotropic hormone, corticosteroids, and vigabatrin are the first-line drugs for the treatment of IS. In children with tuberous sclerosis complex, vigabatrin is the treatment of first choice. Ketogenic diet, sulthiame, topiramate, valproate, zonisamide, and benzodiazepines can be used when first-line drugs have proved ineffective. Children refractory to drug therapy should be evaluated for epilepsy surgery, especially if focal brain lesions are present. Regular follow-up controls, including EEG (preferably sleep EEG) and standardized developmental assessment are recommended. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Multiple source analysis of interictal EEG and MEG spikes was used to identify irritative zones in polymicrogyria (PMG). Spike onset times and source localization were compared between both modalities. PMG is characterized by a marked loss of deep cortical fissures. Hence, differences between EEG and MEG were expected since MEG signals are predominantly generated from tangentially orientated neurons in fissures. Patients: We studied 7 children and young adults (age 7.5 to 19 years) with localization-related epilepsy and unilateral polymicrogyria (PMG) as defined from anatomical MRI. Methods: 122-channel whole-head MEG and 32-channel EEG were recorded simultaneously for 25 to 40 min. Using the BESA program, interictal spikes were identified visually and used as templates to search for similar spatio-temporal spike patterns throughout the recording. Detected similar spikes (r > 0.85) were averaged, high-pass filtered (5 Hz) to enhance spike onset, and subjected to multiple spatio-temporal source analysis. Source localization was visualized by superposition on T1-weighted MRI and compared to the lesion. Results: Nine spike types were identified in seven patients (2 types in 2 patients). Eight out of nine EEG sources and seven MEG sources modeling spike onset were localized within the visible lesion. EEG spike onset preceded MEG significantly in two spike types by 19 and 25 ms. This was related to radial onset activity in EEG while MEG localized propagated activity. In one case, the earliest MEG spike activity was localized to the normal hemisphere while the preceding radial EEG onset activity was localized within the lesion. Distances between EEG and MEG onset sources varied markedly between 9 and 51 mm in the eight spike types with concordant lateralization. Conclusion: Interictal irritative zones were localized within the lesion in PMG comparable to other malformations, e.g., FCD. Discrepancies in MEG and EEG were related to the lack of deep fissures in PMG. In two cases, MEG was blind to the onset of radial interictal spike activity and localized propagated spike activity. In two other cases, MEG localized to the more peripheral parts of the irritative zone. Simultaneous EEG recordings with MEG and multiple source analysis are required to avoid problems of MEG interpretation. [Copyright &y& Elsevier]

Purpose: Simultaneous interictal EEG and magnetoencephalography (MEG) recordings were used for noninvasive analysis of epileptogenicity in focal cortical dysplasia (FCD). The results of two different approach methods (multiple source analysis of averaged spikes and single dipole peak localization of single spikes) were compared with pre- and postoperative anatomic magnetic resonance imaging (MRI). Patients: We studied nine children and adolescents (age, 3.5–15.9 years) with localization-related epilepsy and FCD diagnosis based on MRI. Five patients underwent epilepsy surgery, two of them after long-term recording with subdural grid electrodes, and one after intraoperative electrocorticography. Methods: The 122-channel whole-head MEGs and 33-channel EEGs were recorded simultaneously for 25 to 40 min. Interictal spikes were identified visually and used as templates to search for similar spatiotemporal spike patterns throughout the recording. With the BESA program, similar spikes ( r > 0.85) were detected, averaged, high-pass filtered (5 Hz) to enhance spike onset, and subjected to multiple spatiotemporal source analysis with a multishell spherical head model. Peak activity from single spikes was modeled by single dipoles for the same subset of spikes. Source localization was visualized by superposition on T1-weighted MRI and compared with the lesion identified in T1- and T2-weighted MRI. In the five cases undergoing epilepsy surgery, the results were correlated with invasive recordings, postoperative MRI, and outcome. Results: In all cases, the analysis of averaged spikes showed a localization of onset- and peak-related sources within the visible lesion for both EEG and MEG. Of the single spikes, 128 (45%; total 284) were localizable at the peak in MEG, and 170 (60%) in EEG. Of these, 91% localized within the lesion with MEG, and 93.5% with EEG. In three of five patients operated on, the resected area included the onset zones of averaged EEG and MEG spike activity. These patients had excellent postoperative outcome, whereas the others did not become seizure free. Conclusions: Consistent MEG and EEG spike localization in the lesional zone confirmed the hypothesis of intrinsic epileptogenicity in FCD. [ABSTRACT FROM AUTHOR]