Efficacy of ketogenic diet for infantile spasms: A systematic review.

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.

Midazolam vs diazepam in prolonged seizures in children: A pharmacoeconomic approach.

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.

Electroclinical findings and long-term outcomes in epileptic patients with inv dup (15).

OBJECTIVE: To define the electroclinical phenotype and long-term outcomes in a cohort of patients with inv dup (15) syndrome. MATERIAL AND METHODS: The electroclinical data of 45 patients (25 males) affected by inv dup (15) and seizures were retrospectively analysed, and long-term follow-up of epilepsy was evaluated. RESULTS: Epilepsy onset was marked by generalized seizures in 53% of patients, epileptic spasms in 51%, focal seizures in 26%, atypical absences in 11% and epileptic falls in 9%. The epileptic syndromes defined were: generalized epilepsy (26.7%), focal epilepsy (22.3%), epileptic encephalopathy with epileptic spasms as the only seizure type (17.7%) and Lennox-Gastaut syndrome (33.3%). Drug-resistant epilepsy was detected in 55.5% of patients. There was a significant higher prevalence of seizure-free patients in those with seizure onset after the age of 5 years and with focal epilepsy, with respect to those with earlier epilepsy onset because most of these later developed an epileptic encephalopathy (69.2% vs 34.4%; P = .03), usually Lennox-Gastaut Syndrome in type. In fact, among patients with early-onset epilepsy, those presenting with epileptic spasms as the only seizure type associated with classical hypsarrhythmia achieved seizure freedom (P < .001) compared to patients with spasms and other seizure types associated with modified hypsarrhythmia. CONCLUSIONS: Epilepsy in inv dup (15) leads to a more severe burden of disease. Frequently, these patients show drug resistance, in particular when epilepsy onset is before the age of five and features epileptic encephalopathy.

Clinical dissection of childhood occipital epilepsy of Gastaut and prognostic implication.

BACKGROUND AND PURPOSE: Our aim was to describe the clinical and electrical features and the long-term evolution of childhood occipital epilepsy of Gastaut (COE-G) in a cohort of patients and to compare long-term prognosis between patients with and without other epileptic syndromes. METHODS: This was a retrospective analysis of the long-term outcome of epilepsy in 129 patients with COE-G who were referred to 23 Italian epilepsy centres and one in Austria between 1991 and 2004. Patients were evaluated clinically and with electroencephalograms for 10.1-23.0 years. The following clinical characteristics were evaluated: gender, patient age at seizure onset, history of febrile seizures and migraine, family history of epilepsy, duration and seizure manifestations, circadian distribution and frequency of seizures, history of medications including the number of drugs, therapeutic response and final outcome. RESULTS: Visual hallucinations were the first symptom in 62% and the only manifestation in 38.8% of patients. Patients were subdivided into two groups: group A with isolated COE-G; group B with other epileptic syndromes associated with COE-G. The most significant (P < 0.05) difference concerned antiepileptic therapy: in group A, 45 children responded to monotherapy; in group B only 15 children responded to monotherapy. At the end of follow-up, the percentage of seizure-free patients was significantly higher in group A than in group B. CONCLUSIONS: Childhood occipital epilepsy of Gastaut has an overall favourable prognosis and a good response to antiepileptic therapy with resolution of seizures and of electroencephalogram abnormalities. The association of typical COE-G symptoms with other types of seizure could be related to a poor epilepsy outcome.

Prognostic factors in children with PRES and hematologic diseases.

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.

Headache, migraine and obesity: an overview on plausible links.

Headache can represent different disorders with different etiologies; including cardiac, cerebral, vascular, psychiatric, metabolic, neurologic diseases. Recent studies have highlighted that obesity is significantly associated with headache and disability in adults. This rule also applies to children. This review focuses on literature data studying any eventual relationship between headache, migraine and obesity [shown in Body Mass Index (BMI)] in children. Research data have highlighted that there is a relationship between headache physiopathology and central and peripheral mechanisms responsible for food assumption. In this regard, neurotransmitters such as serotonin, and peptides such as orexin and adipocytokines (adiponectin and leptin) seem to play a key role both in food assumption and in headache pathogenesis. These data further emphasize the potential association between headache and BMI. Therefore, those therapeutic strategies aiming to decrease BMI may represent a model of useful treatment to understand whether weight loss reduces the incidence and the severity of headache in obese children. In conclusion, considering the effects of obesity and weight loss on the natural history of headache, important changes are expected in therapeutic management of paediatric headaches.

Children with developmental dyslexia showed greater sleep disturbances than controls, including problems initiating and maintaining sleep.

AIM: Although there have been frequent clinical reports about sleep disturbances in children with learning disabilities, no data are available about the prevalence of sleep disturbances in children with developmental dyslexia (DD). This study evaluated sleep disturbances in children with DD referred to a hospital clinic and compared their scores with healthy controls. METHODS: We consecutively enrolled 147 children (66% male) aged 10.26 ± 2.63 years who were referred by clinical paediatricians to the Clinic for Child and Adolescent Neuropsychiatry at the Second University of Naples with DD and 766 children without DD (60% male) aged 10.49 ± 2.39 years recruited from schools in the same urban area. Sleep disturbances were assessed with the Sleep Disturbances Scale for Children (SDSC), which was filled out by the children's main carers. RESULTS: Compared with the controls, the children with DD showed significantly higher rates of above threshold scores on the total SDSC score (p < 0.001) and on the subscales for disorders in initiating and maintaining sleep (p < 0.001), sleep breathing disorders (p < 0.001) and disorders of arousal (p < 0.001). CONCLUSION: Sleep disorders were significantly more frequent in children with DD than in healthy controls. A possible relationship between dyslexia and sleep disorders may have relevant clinical implications.

EMERGING AND FUTURE THERAPIES FOR ALLERGIC RHINITIS.

Allergic rhinitis (AR) is one of the most common diseases and represents a global health problem, currently affecting up to 30% of the general population, with a continuously increasing prevalence and significant comorbidities and complications. To date, the mainstay of current treatment strategies of AR includes allergen avoidance, pharmacotherapy and allergen-specific immunotherapy, as defined by Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines for both adults and children. The aim of this review is to provide an update on all emerging and future therapeutic options for the treatment of AR.

Genital ulcer as a new clinical clue to PFAPA syndrome.

Vaginal ulcers can be associated with a number of different diseases. We describe two girls who presented genital ulcers as a persistent symptom of PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome. The possibility of considering this clinical manifestation as a clue for the diagnosis of PFAPA is discussed.

MYOCLONIC ASTATIC EPILEPSY IN A PATIENT WITH A DE NOVO 4q21.22q21.23 MICRODUPLICATION.

Myoclonicastatic epilepsy (MAE) is a rare form of symptomatic generalized epilepsy of uncertain etiology. To search the possible genetic basis of the disorder, here we investigate a 15 year-old patient with MAE, who is the only person presenting epilepsy in the family. High resolution array-CGH analysis was conducted on DNA extracted from peripheral blood of the patient and the parents. The copy number variant(s) (CNVs) identified were further confirmed by Fluorescent In Situ Hybridization (FISH). The array-CGH identified a de novo microduplication of about 778 Kb in the chromosome region 4q21.22-q21.23, involving 11 genes. This is the first report of a de novo CNV in MAE. The genes involved in the duplication are potential candidates that can be investigated in the future to determine their exact role in the etiopathogenesis of the disorder. However, we suggest performing microarray chromosomal analysis in patients with MAE, since rare de novo CNVs could be identified, and this is known to affect the diagnostic process and recurrence risk assessment.

Efficacy and tolerability of add-on lacosamide in children with Lennox-Gastaut syndrome.

OBJECTIVE: Available data on the efficacy of lacosamide in children with Lennox-Gastaut syndrome (LGS) are scarce and controversial. We present our experience with lacosamide therapy in children affected by LGS. MATERIAL AND METHODS: Medical charts of all children affected by LGS receiving oral lacosamide adjunctive therapy in six paediatric neurology centres were retrospectively evaluated. Efficacy was determined according to the frequency of countable seizures during the 4 weeks prior to treatment and the frequency in the last 4 weeks of observation. Patients whose seizure frequency was reduced by at least 50% were defined as responders. RESULTS: Eighteen children (mean age 12.3 years) were identified. After a mean follow-up period of 9 months, 33% of patients were responders. None of them was seizure-free during the study period. The overall seizure reduction rate was 29%. The percentage reductions from baseline in tonic seizures and drop-attacks rates were 31% and 20%, respectively. Adverse reactions occurred in 44% of patients. The drug was discontinued in four (22%) patients because of increased seizure frequency (three cases) and walking instability (another patient). CONCLUSIONS: A third of children with LGS were responders after lacosamide adjunctive therapy. Although caution is still necessary when the drug is used in children with LGS, our preliminary observations suggest that lacosamide might be effective and represent a possible therapeutic option in children affected by LGS.

Childhood obesity: prevention and strategies of intervention. A systematic review of school-based interventions in primary schools.

PURPOSE: Two crucial aspects of obesity prevention are early childhood and school-based interventions. The main purpose of this systematic review wass to evaluate the efficacy and the feasibility of school-based interventions performed in primary schools. METHODS: All pertinent data from the literature have been critically examined and reviewed to evaluate the efficacy and the feasibility of different strategies of interventions. In particular, many studies have been performed in school-aged children. RESULTS: Data from literature suggest that educational interventions toward healthy eating habits and physical activity at school could be a key strategy in the prevention of obesity, because it has been shown that is difficult to treat obesity in adults through changes in the lifestyle rather than during childhood. Recent advances in technology, especially web-based interventions, have been used to provide a specific content addressing healthy lifestyle with regard diet and exercise. These data suggest the opportunity to use web-interactive programs as a new challenging technique of communication in order to promote healthy behaviors. CONCLUSIONS: The early detection and treatment of obesity in children may be the best approach to prevent future increases in morbidity, as well as healthcare costs that will likely occur as overweight and obese children age.

Anticonvulsant drugs and hematological disease.

Many antiepileptic drugs (AEDs) are associated with hematological disorders that range from mild thrombocytopenia or neutropenia to anemia, red cell aplasia, until bone marrow failure. Fortunately, potentially fatal hematological disorders such as aplastic anemia are very rare. This review investigates hematological effects associated with classic and newer AEDs: a PubMed search indexed for MEDLINE was undertaken to identify studies in adults, children and animals using the name of all anticonvulsant drugs combined with the terms "hematological disease" and "hematological abnormalities" as key words. The most common hematological alterations occur with older AEDs than newer. Indeed, careful hematological monitoring is needed especially using carbamazepine, phenytoin and valproic acid. The pathogenetic mechanisms are still unknown: they seem to be related to an immunological mechanism, but drugs pharmacokinetics and pharmacodynamics interactions may also play an important role. Further research is needed to assess the real pathogenetic mechanism at the basis of hematological complications caused by AEDs.

The adverse event profile of perampanel: meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: To identify adverse events (AEs) significantly associated with perampanel treatment in double-blind clinical studies (RCTs). Serious AEs, study withdrawals due to AEs and dose-effect responses of individual AEs were also investigated. METHODS: All placebo controlled, double-blind RCTs investigating therapeutic effects of oral perampanel were searched. AEs were assessed for their association with perampanel after exclusion of synonyms, rare AEs and non-assessable AEs. Risk difference (RD) was used to evaluate the association of any AE (99% confidence intervals) and withdrawals or serious AEs (95% confidence intervals) with perampanel. RESULTS: Nine RCTs (five in pharmacoresistant epilepsy and four in Parkinson's disease) were included in our study. Almost 4000 patients had been recruited, 2627 of whom were randomized to perampanel and treated with drug doses of 0.5 mg/day (n = 68), 1 mg/day (n = 65), 2 mg/day (n = 753), 4 mg/day (n = 1017), 8 mg/day (n = 431) or 12 mg/day (n = 293). Serious AEs were not significantly associated with perampanel treatment. The experimental drug was significantly associated with an increased risk of AE-related study withdrawals at 4 mg/day [RD (95% confidence interval) 0.03 (0.00, 0.06)] and 12 mg/day [RD (95% confidence interval) 0.13 (0.07, 0.18)]. Of 15 identified AEs, five (dizziness, ataxia, somnolence, irritability and weight increase) were found to be significantly associated with perampanel and one (seizure worsening) was significantly associated with placebo. CONCLUSIONS: Vestibulocerebellar AEs (dizziness, ataxia), sedative effects (somnolence), irritability and weight increase were significantly associated with perampanel treatment.

Impact of a weight loss program on migraine in obese adolescents.

BACKGROUND AND PURPOSE: Increased headache frequency and severity have been observed in obese populations, but the real impact of a weight loss treatment on headache has not been studied. We investigated this issue in a sample of obese adolescents. METHODS: In all, 135 migraineurs, aged 14-18 years, with body mass index (BMI) ≥ 97 th percentile, participating in a 12-month-long program, were studied before and after treatment. The program included dietary education, specific physical training, and behavioral treatment. RESULTS: Decreases in weight (P < 0.01), BMI (P < 0.01), waist circumference (P < 0.01), headache frequency (P < 0.01) and intensity (P < 0.01), use of acute medications (P < 0.05), and disability (P < 0.05) were observed at the end of the first 6-month period and were maintained through the second 6 months. Both lower baseline BMI and excess change in BMI were significantly associated with better migraine outcomes 12 months after the intervention program. CONCLUSIONS: Significant improvements in both adiposity and headache data were observed in obese adolescents with migraine who participated in a 12-month-long interdisciplinary intervention program for weight loss. Initial body weight and amount of weight loss may be useful for clinicians to predict migraine outcomes.

Early-onset absence epilepsy: SLC2A1 gene analysis and treatment evolution.

BACKGROUND AND PURPOSES: To determine the prevalence of SLC2A1 mutations in children with early-onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure-free with anti-epileptic drug (AED) monotherapy (group I) and those who needed add-on treatment of a second AED (group II). METHODS: We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of SLC2A1 was performed in each patient. RESULTS: Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in SLC2A1 was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first-degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month follow-up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II (P = 0.008). CONCLUSIONS: We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure-free with add-on treatment of a second AED.

The adverse event profile of zonisamide: a meta-analysis.

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.

Otorrhea in Kawasaki disease diagnosis complicated by an EBV infection: coincidental disease or a true association.

The Authors report on two children affected by Kawasaki disease (KD). The diagnosis of KD was made after exclusion of conditions with similar presentation. At admission these children (cases 1 and 2) presented fever, purulent caseous pharyngotonsillitis, and cervical bilateral lymphadenopathy, as well as an erythematous non-vesicular rash over the face and trunk, and a mild bilateral non-exudative conjunctivitis in case 1. After respectively three and two days corticosteroid therapy was started without any significant improvement of the general condition and any diminutions of the fever. Two days later in case 1 the child presented a clear otorrhea, a cutaneous non vesicular rash, and soon after all the remaining signs of Kawasaki disease, in case 2 otorrhea was found after 4 days and then the other signs of the KD. These patients were treated with intravenous immunoglobulin (2 g/kg day), with an improvement of their general condition. To our knowledge we report the first cases of otorrhea in the setting of Kawasaki disease. We cannot exclude that the presence of Kawasaki disease in the context of otorrhea in children positive for Epstein-Barr virus (EBV) is merely coincidental. Besides, recent acquisitions show that KD is due to a new virus that could cross-react with the EBV. The Authors conclude that the presence of EBV infection or similar condition in a febrile child may not exclude Kawasaki disease and a differential diagnosis has to be performed for a timely commencement of intravenous immunoglobulin therapy.  

Effects of anti-epileptic drugs on the oral health of paediatric patients.

AIM: To evaluate the effects of epilepsy therapy on the oral health in paediatrics patients. MATERIALS: The test has involved 57 patients. The patients were stratified in three groups: monotherapy group, politherapy group and control group. They were examined and after that the test groups were compared with the control group. CONCLUSION: Paediatric epileptic patients seem to have a greater risk of having a worse oral health status compared with healthy patients. However, if the patient is well monitored and undergoes regular dental checks, the oral condition is comparable to a healthy subject.

Acquired peripheral neuropathy: a report on 20 children.

Guillain-Barré syndrome (GBS) is an inflammatory polyneuropathy characterized by acute onset, rapid progression, symmetric muscular weakness, pain, and paresthesias. The incidence of GBS in the pediatric age group is 0.8 cases per 100,000; 50%-70% of the cases are preceded by respiratory or gastrointestinal infectious episodes or vaccination. The etiopathogenesis of GBS has been hypothesized to involve a direct immune-mediated mechanism against the peripheral nerves. A series of 20 patients managed in the Department of Pediatrics of the University of Catania between 2003 and 2011 and evaluated according to epidemiologic, clinical, and therapeutic features is reported.