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The aim of this systematic review was to collect and analyze all the RCTs and observational studies investigating the efficacy of ketogenic diet (KD) in infantile spasms (IS) patients after a 1- to 6-month follow-up period, in terms of decrease in seizure frequency of >50% or a seizure-free interval. Moreover, the potential effect of gender, IS etiology, age at onset of IS, and age at start of KD have been investigated. Finally, we evaluated the seizure-free rate at 12 and 24 months of follow-up. In June 2016, a computer search was performed on MedLine (PubMed), EMBASE, and the Cochrane Library. Only, English language studies conducted after 1980 and those reporting in detail the variation in seizure frequency have been selected. Thirteen observational studies (341 patients) were included in the final analysis. A median rate of 64.7% of patients experienced a spasm reduction >50% (IQR: 38.94%). The median spasm-free rate was 34.61% (IQR: 37.94%). IS of unknown etiology seemed to have an increased probability of achieving freedom from seizures (RR: 1.72, 95%CI: 1.18-2.53). Long-time follow-up data revealed a median seizure-free rate of 9.54% (IQR: 18.23%). Although the literature is still lacking in high-quality studies, which could provide a stronger level evidence, our findings suggest a potential benefit of KD for drug-resistant IS patients.

Objective A previous European cost-utility study reported that use of buccal midazolam in the community setting for the treatment of prolonged seizures (ie, seizures lasting ≥5 minutes) in children was associated with an overall €12 507 399 reduction in annual costs charged to the Italian national health service compared with rectal diazepam. We re-evaluated these findings by applying a more conservative approach. Methods The Italian Delphi panel reconvened to apply a more conservative assessment of available reports. A decision-tree model was used, allowing for different treatment pathways depending on whether or not a caregiver administers treatment, an ambulance is required for transport of the child to hospital, and an inpatient stay is required. Direct medical costs were derived from Italian healthcare system data. Estimates of the annual number of prolonged tonic-clonic seizures expected in the country were based on studies which assessed seizure duration using video-EEG recordings and medical records. Results Although drug acquisition costs were greater for buccal midazolam than for rectal diazepam, the acquisition cost difference was outweighed by larger cost savings resulting mostly from a reduction in hospital admissions. Assuming that 1.2% of tonic and/or clonic seizures occurring in children and adolescents over a 12-month period are prolonged, the annual nationwide reduction in costs from preferring buccal midazolam to rectal diazepam was estimated at €3 577 587.9. Conclusions In this more conservative revised analysis, the high cost of buccal midazolam is still counteracted by greater cost savings compared with rectal diazepam, but cost reduction was less than previously estimated.

Objectives Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterized by focal neurological signs, headache, confusion, and seizure, associated with transitory lesions in the posterior areas of the brain detectable with neuroimaging. Among children, one of the most common causes of PRES is cancer. Materials and Methods In this review, we present the cases of 5 children developing PRES after stem cell transplantation for hematological disease and review all the cases reported in English literature to investigate outcomes and associated risk factors. Results One hundred and eleven cases were reported. Hypertension was very frequent (80%). Clinical features included seizures (80.1%), headache (44.1%), visual disturbance (26.1%), and mental change (48.6%). EEG was abnormal in 27 of 32 patients. MRI revealed characteristic lesions in all patients even in early stages. Abnormal MRI findings in late stages were associated with neurological sequelae. Nineteen patients died (17.1%) of which 2 of PRES. Among alive patients, 17 had neurological sequelae. Four cases of PRES relapse were described. Conclusions Thus, all transplant recipients with symptoms consistent with PRES should be promptly recognized to avoid long-term complications or even death.

Verrotti A, Nanni G, Agostinelli S, Tozzi Alleva E, Aloisi P, Franzoni E, Spalice A, Chiarelli F, Coppola G. Effects of the abrupt switch from solution to modified-release granule formulation of valproate. Acta Neurol Scand: 2012: 125: e14–e18. © 2011 John Wiley & Sons A/S. Background – A new modified-release (MR) granule formulation of valproate (VPA) has been recently developed for the treatment of children with epilepsy. It consists of tasteless microspheres that can be sprinkled on soft foods and easily swallowed. There are no data on the effectiveness of this formulation in pediatric age. Aim of the study – To evaluate the effects of the abrupt switch from solution to VPA MR granules in children undergoing chronic treatment. Methods – We enrolled children receiving VPA solution as sole or adjunctive therapy and switched them to MR granules at identical dosages. VPA blood level, treatment efficacy (clinical and EEG data), tolerability (adverse reactions), palatability, ease of administration, and compliance were evaluated before switching (T0) and after 4 weeks (T1). Results – Out of 112 enrolled children, 108 (96.4%) completed the evaluation. We observed no significant differences between the patients at T0 and T1 in VPA blood levels, treatment efficacy, tolerability, and compliance. MR granules were judged more palatable (P

The first aim of our study was to analyze the adverse events statistically significantly associated with zonisamide, through a systematic review and meta-analysis of available randomized placebo-controlled trials (RCTs). The second aim was to compare these results with those obtained from an analysis of non-RCTs and observational studies. Randomized controlled trials were identified using Medline (PubMed), EMBASE (Ovid), and Cochrane CENTRAL, from 1990 to September 2012. RevMan version 5.1 and OpenMeta[Analyst] were used for analyses of RCT and non-RCTs, respectively. Six eligible studies with 1184 patients between 12 and 80 years of age were included in RCTs analysis. Fifteen adverse events were investigated. In this first part of the analysis, no adverse events were statistically significantly associated with zonisamide. In the non-RCT analysis, a high incidence of weight loss and headache was found. In RCTs, zonisamide was statistically significantly associated with an increased risk of adverse event-related study withdrawals [RR (99% CI) = 1.81 (1.07-3.08)]. Although our study revealed no statistically significantly associated adverse effects (AEs) with zonisamide, this is very likely a consequence of the small numbers in the RCTs available. The limited data available from the studies appear to reveal no major safety concerns related to zonisamide. However, the high incidence of weight loss and headache in the non-RCTs suggests that these AEs could be of clinical significance.

Grosso S, Coppola G, Cusmai R, Parisi P, Spalice A, Foligno S,Verrotti A, Balestri P. Efficacy and tolerability of add-on lacosamidein children with Lennox-Gastaut syndrome.Acta Neurol Scand: DOI: 10.1111/ane.12221.© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Objective – Available data on the efficacy of lacosamide in childrenwith Lennox-Gastaut syndrome (LGS) are scarce and controversial.We present our experience with lacosamide therapy in childrenaffected by LGS. Material and Methods – Medical charts of allchildren affected by LGS receiving oral lacosamide adjunctive therapyin six paediatric neurology centres were retrospectively evaluated.Efficacy was determined according to the frequency of countableseizures during the 4 weeks prior to treatment and the frequency inthe last 4 weeks of observation. Patients whose seizure frequency wasreduced by at least 50% were defined as responders. Results –Eighteen children (mean age 12.3 years) were identified. After a meanfollow-up period of 9 months, 33% of patients were responders. Noneof them was seizure-free during the study period. The overall seizurereduction rate was 29%. The percentage reductions from baseline intonic seizures and drop-attacks rates were 31% and 20%, respectively.Adverse reactions occurred in 44% of patients. The drug wasdiscontinued in four (22%) patients because of increased seizurefrequency (three cases) and walking instability (another patient).Conclusions – A third of children with LGS were responders afterlacosamide adjunctive therapy. Although caution is still necessarywhen the drug is used in children with LGS, our preliminaryobservations suggest that lacosamide might be effective and representa possible therapeutic option in children affected by LGS.

The aim of this study was to assess how the ketogenic diet influences the blood levels of antiepileptic drugs in the first month of treatment in a pediatric population with drug-resistant epilepsy.The plasma concentrations of antiepileptic drugs were investigated in an open study on 36 consecutive children and adolescents (20 males), aged between 6 months and 16 years (mean age 4.7 years), who were put on the ketogenic diet because of medically refractory epilepsy. The plasma levels of antiepileptic drugs were determined 30 days and immediately before the diet and on days 8, 15, 22 and 29 after the start of the diet. The daily dose of each drug was not changed during the first month of treatment, while the daily dose of benzodiazepines was reduced by up to 30% if excessive sedation or drowsiness occurred.While plasma concentrations of phenobarbital did not change in the first month on the ketogenic diet (mean increase of 2.3 mg/l ± 1.0), valproic acid showed a slight but not significant decrease (mean decrease of 6.7 mg/l ± 3.2), 2 weeks after the start of the diet.Adjustments in the daily dose of either drug before the start of the diet do not however appear to be justified.

Coppola G, Verrotti A, D’Aniello A, Arcieri S, Operto FF, Della Corte R, Ammendola E, Pascotto A. Valproic acid and phenobarbital blood levels during the first month of treatment with the ketogenic diet. Acta Neurol Scand: 2010: 122: 303–307. © 2010 John Wiley & Sons A/S. Objective – The aim of this study was to assess how the ketogenic diet influences the blood levels of antiepileptic drugs in the first month of treatment in a pediatric population with drug-resistant epilepsy. Methods – The plasma concentrations of antiepileptic drugs were investigated in an open study on 36 consecutive children and adolescents (20 males), aged between 6 months and 16 years (mean age 4.7 years), who were put on the ketogenic diet because of medically refractory epilepsy. The plasma levels of antiepileptic drugs were determined 30 days and immediately before the diet and on days 8, 15, 22 and 29 after the start of the diet. The daily dose of each drug was not changed during the first month of treatment, while the daily dose of benzodiazepines was reduced by up to 30% if excessive sedation or drowsiness occurred. Results – While plasma concentrations of phenobarbital did not change in the first month on the ketogenic diet (mean increase of 2.3 mg/l ± 1.0), valproic acid showed a slight but not significant decrease (mean decresase of 6.7 mg/l ± 3.2), 2 weeks after the start of the diet. Conclusions – Adjustments in the daily dose of either drug before the start of the diet do not however appear to be justified.

To evaluate the photoparoxysmal responses (PPR) in non-epileptic children and adolescents in long-term follow-up.We studied 14 non-epileptic children who showed PPR without any other electroencephalographic (EEG) abnormalities.One subjects was lost after 1 year of follow-up. At the final follow-up, four of the 13 patients (approximately 30%) did not show any PPR or other epileptic discharges, while in other children PPR continued to be present. The age of the disappearance of PPR in these four patients ranged from 1.1 to 5.9 years from the first evaluation. No patients suffered from epileptic seizures during the whole period of follow-up.Our study confirms that PPR can be present in the EEG of non-epileptic children and adolescents and demonstrates that this EEG change is not related to the presence of seizures and must not be considered a marker for the developing of epilepsy.