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Objective: To report a prospectively planned analysis of two randomised controlled trials with embedded comparisons of prednisolone versus tetracosactide depot for the treatment of infantile epileptic spasms syndrome (IESS)., Methods: Individual patient data from patients randomly allocated to prednisolone or tetracosactide depot were analysed from two trials (UKISS, ICISS). The comparison was embedded within trials in which some patients also received vigabatrin but only patients receiving monotherapy with randomly allocated hormonal treatments are included in this analysis. The main outcome was cessation of spasms (Days 13-14 after randomisation). Lead time to treatment and underlying aetiology were taken into account. Cessation of spasms on Days 14-42 inclusive, electroclinical response (EEG Day 14), plus developmental and epilepsy outcomes (at 14 months in UKISS and 18 months in ICISS) are also reported. Minimum treatment was prednisolone 40 mg per day for two weeks or tetracosactide depot 0·5 mg IM on alternate days for two weeks, all followed by a reducing dose of prednisolone over two weeks., Results: 126 infants were included in this study. On tetracosactide depot, 47 of 62 (76%) were free of spasms on Days 13-14 compared to 43 of 64 (67%) on prednisolone (difference 9%, 95% CI -7·2% to +25·2%, chi square 1·15, p = 0·28). For Day 14-42 cessation of spasms, on tetracosactide depot, 41 of 61 (67%) were free of spasms compared to 35 of 62 (56%) on prednisolone (difference 11%, 95% CI -6·4% to +28·4%, chi square 1·51, p = 0·22). There was no significant difference in mean VABS score between infants who received prednisolone compared with those who received tetracosactide depot (74·8 (SD 18·3) versus 78·0 (SD 20·2) t = -0·91 p = 0·36). The proportion with ongoing epilepsy at the time of developmental assessment was 20 of 61 (33%) in the tetracosactide group compared with 26 out of 63 (41%) in the prednisolone group (difference 8%, 95% CI -9·2% to +25·2%, Chi [2] 0·95, p = 0·33)., Significance: With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome., Competing Interests: Declaration of competing interest JPO unsuccessfully approached Aventis for funding of a follow up study to look at visual field defects: he appeared in a promotional video for Aventis: he received income from UCB Pharma. The study sponsor for UKISS and ICISS received funding from Marathon and from UCB Pharma which was used in part to fund the research reported including salaries to JPO and SE. JPO, SE, FJKOC, EH and AL all received IP payments from the sponsor relating to funding from Marathon. AL received funding from Hoechst-Marion-Roussel to attend a conference. No other authors declared a conflict of interest., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

To evaluate and manage epileptic seizures and other paroxysmal events in infants, it is necessary to ask five key questions: (1) Is this a type of epilepsy?; (2) What seizure type(s) are occurring?; (3) Do these seizure types, combined with factors such as age at onset and EEG features, constitute an 'epilepsy syndrome'?; (4) What investigations do we need to do in searching for an underlying aetiology? and finally, (5) What is the prognosis for neurological and developmental state in later life? This review considers epilepsies that have an onset in infancy but after the perinatal period, outlines the commoner epilepsy syndromes occurring in this age group and describes paroxysmal events that can mimic epilepsy. Epilepsies in infancy may be the manifestation of a genetic predisposition associated with a benign course and good prognosis for neurodevelopment. In contrast, they may pose the challenging situation of 'epileptic encephalopathy', rare but potentially treatable metabolic conditions, or structural abnormalities with poor developmental outlook and intractable seizures. Seizures in infancy are relatively rare and there is a wide range of underlying causes, some of which require specific treatments to avoid preventable neurodevelopmental damage. Guidance from the National Institute for Health and Clinical Excellence suggests early referral of cases of infantile epilepsy to a tertiary centre.

Background: Infantile spasms is a severe infantile seizure disorder that is difficult to treat and has a high morbidity. Absence of spasms on days 13 and 14 after randomisation is more common in infants allocated hormone treatments than in those allocated vigabatrin. We sought to assess whether early control of spasms is associated with improved developmental or epilepsy outcomes., Methods: Infants enrolled in the United Kingdom Infantile Spasms Study (UKISS) were randomly assigned hormone treatment (n=55) or vigabatrin (n=52) and were followed up until clinical assessment at 12-14 months of age. We assessed neurodevelopment with the Vineland adaptive behaviour scales (VABS) at 14 months of age on an intention to treat basis., Findings: Of 107 infants enrolled, five died and 101 survivors reached both follow-up assessments. Absence of spasms at final clinical assessment (hormone 41/55 [75%] vs vigabatrin 39/51 [76%]) was similar in each treatment group (difference 1.9%, 95% CI -18.3% to 14.4%; chi(2)=0.05; p=0.82). Mean VABS score did not differ significantly (hormone 78.6 [SD 16.8] vs vigabatrin 77.5 [SD 12.7]; difference 1.0, 95% CI -4.9 to 7.0; t(99)=0.35, p=0.73). In infants with no identified underlying aetiology, the mean VABS score was higher in those allocated hormone treatment than in those allocated vigabatrin (88.2 [17.3] vs 78.9 [14.3]; difference 9.3, 95% CI 1.2 to 17.3; t(95)=2.28, p=0.025)., Interpretation: Hormone treatment controls spasms better than does vigabatrin initially, but not at 12-14 months of age. Better initial control of spasms by hormone treatment in those with no identified underlying aetiology may lead to improved developmental outcome.