Maria Gogou

Sleep apneas and epilepsy comorbidity in childhood: a systematic review of the literature

PurposeOur aim is to review studies which assess the prevalence of sleep apneas in children with epilepsy and discuss possible mechanisms linking these two conditions, as well as the impact of sleep apneas on the prognosis of these children.MethodsPubMed was used as the medical database source, and articles were selected and classified according to their originality, level of evidence, and relevance to the broad scope of the review.ResultsChildren with epilepsy have a higher prevalence of sleep breathing disorders in comparison to healthy children, but this prevalence varies widely depending on the methodology of each study. Major risk factors for sleep apneas in childhood epilepsy include mainly poor seizure control and antiepileptic drug polytherapy. Indeed, epilepsy can trigger sleep apneas, as abnormal electrical discharge amplifies sleep-induced breathing instability, antiepileptic drugs disturb muscle tone, and vagus nerve stimulation modulates neurotransmission to airway muscles. On the other hand, sleep apneas enhance sleep fragmentation, thus reducing the threshold for the appearance of seizures. Moreover, they have a negative effect on the neurocognitive profile of these children, as they disturb neuroplasticity mechanisms and also have a probable association with sudden unexpected death in epilepsy. The surgical treatment of sleep apneas has been found to reduce seizure frequency, and this can offer new therapeutic choices.ConclusionsBetween sleep apneas and childhood epilepsy, there is a complex relationship with reciprocal interactions. The presence of sleep apneas should be taken into account when designing the management of these children, as it creates therapeutic opportunities and limitations.

Valproate effect on ketosis in children under ketogenic diet

INTRODUCTION Although ketogenic diet has been proven useful in the management of intractable seizures, interactions with other medicines have been reported. This study reports two patients on co-administration with ketogenic diet and valproate appearing undesirable side effects after increase or decrease of valproate pharmaceutical levels. METHODS Totally 75 patients suffering from drug-resistant epilepsy were treated with ketogenic diet in our departments. Their age varied from 6 months to 9 years. All patients were followed for at least 12 months and up to five years. Clinical and laboratory variables have been regularly assessed. RESULTS In 75 patients treated with ketogenic diet and valproate at the same time treatment was well tolerated. Two patients presented mild to moderate undesirable effects. In these patients the removal of valproate treatment resulted in an increase of ketosis with respective clinical signs. The conversion of the diet from 4:1 to 1:1 and 2,5:1 respectively resulted in reduction of ketosis and clinical improvement. CONCLUSION In the majority of cases co-administration of valproate and ketogenic diet seems to be safe. In two cases, valproate appeared to have a negative effect on ketosis (and weaning it led to over-ketosis). This interaction is worthy of future study.

The effect of dietary supplements on clinical aspects of autism spectrum disorder: A systematic review of the literature.

BACKGROUND Autism spectrum disorder is associated with significant social and financial burden and no definite treatment for this entity has been identified, yet. In recent years there has been an increasing interest in the use of dietary interventions as a complementary therapeutic option for these patients. OBJECTIVE The aim of this systematic review is to provide high evidence level literature data about the effect of dietary supplements on clinical aspects of children with autism. METHODS A comprehensive literature search was conducted using Pubmed as the medical database source. Randomized controlled trials conducted in pediatric populations and including measures of clinical outcomes were considered. RESULTS A total of 17 eligible prospective studies were selected. Types of dietary supplements evaluated in these studies included amino acids, fatty acids and vitamins/minerals. N-acetylcysteine was shown to exert a beneficial effect on symptoms of irritability. On the other hand, literature data about the efficacy of d-cycloserine and pyridoxine-magnesium supplements was controversial. No significant effect was identified for fatty acids, N,N-dimethylglycine and inositol. Literature data about ascorbic acid and methyl B12 was few, although some encouraging results were found. No serious adverse events were reported in the vast majority of the studies, while the prevalence of adverse reactions was similar between treatment and placebo groups. CONCLUSIONS The use of dietary supplements in children with autism seems to be a safe practice with encouraging data about their clinical efficacy. More studies are needed to further investigate this issue.

Clinical Applications of Intravenous Immunoglobulins in Child Neurology

BACKGROUND While there are guidelines for the use of intravenous immunoglobulins in children with Guillain-Barre syndrome and myasthenia gravis based on high-level evidence studies, data are scarce for the majority of neurologic disorders in this age group. Neuronal antibodies are detected in children with seizures of autoimmune etiology. Intravenous immunoglobulins with their broad immunomodulatory mechanism of action could be ideally effective in different forms of immunedysregulated intractable epilepsies such as autoimmune epilepsy and autoimmune Rasmussen encephalitis. We conducted a systematic review of the literature for evidence of the use of intravenous immunoglobulins in a variety of neurologic diseases in childhood. METHOD A comprehensive literature search was conducted using Pubmed as the medical database source without date range. Prospective studies in pediatric groups including objective measures of clinical outcomes were systematically selected. RESULTS A total of 11 prospective studies were identified in the literature demonstrating a favorable effect of this therapeutic option in children with drug-resistant epilepsy and in cases of encephalitis. No serious adverse effects were reported. No prospective studies about the use of intravenous immunoglobulins in children with demyelinating disorders or neurologic paraneoplasmatic syndromes were found. CONCLUSION In this review, we summarize the recent advances in the field of intravenous immunoglobulins used in pediatric neurological diseases. Literature data supports a beneficial effect in this age group. Whilst awaiting the results of large scale studies, administration of intravenous immunoglobulins could be justified in refractory child epilepsy. Otherwise, its use should be guided by the individual needs of each child, depending on the underlying neurological disease.

Succinic Semialdehyde Dehydrogenase Deficiency Presenting as Autism Spectrum Disorder

To the Editor: A 10-y-old boy with autism spectrum disorder (DSM IV criteria) and normal perinatal history presented to our outpatient clinic for investigation. Evaluation revealed declined fine motor development, moderate language development, repetitive behavior, attention deficit and hyperactivity. Common laboratory tests, electroencephalogram and Magnetic Resonance Imaging (MRI) of the brain were normal. The metabolic screening requested revealed an elevated concent ra t ion of 4-hydroxy-buty r ic ac id in ur ine (60.8 mmol/mol creatinine of urine, normal values: 0). Genetic test revealed two pathogenic mutations in the ALDH5A1 gene, thus confirming diagnosis of succinic semialdehyde dehydrogenase deficiency (SSADHD). Treatment with vigabatrin was initiated without clinical improvement. SSADHD is caused by mutations of the ALDH5A1 gene (6p22), resulting in dysfunction of the enzyme succinic semialdehyde dehydrogenase and accumulation of γ-aminobutyric acid, succinic semialdehyde and γhydroxybutyric acid. Clinical features include intellectual disability, seizures, hypotonia, ataxia and behavioral disturbances. Diagnosis is mainly based on urinary organic acid analysis and genetic testing [1]. MRI of the brain often demonstrates globus pallidii signal changes and cerebellar atrophy [2]. Clinical studies about the impact of vigabatrin, sodium valproate and taurine on clinical aspects of the disease have controversial results [1]. The patient presented autism as the only symptom. This raises the question if metabolic screening should be requested for children with autism spectrum disorder. Schiff et al. found that a routine metabolic screening does not contribute to the causative diagnosis of autism, as the prevalence of inborn metabolic errors in nonsyndromic autism may not be higher than in the general population [3]. On the other hand, in a Greek cohort study of 187 children with confirmed autistic features, who underwent detailed metabolic screening, specific metabolic biomarkers were revealed in 5 of them (2, 7 %) with therapeutic relevance [4]. The underlying cause of autism is often elusive with the exception of recognizable genetic syndromes [3]. The identification of a specific cause at an early age is important for initiating effective individualized intervention and permits genetic counseling. * Maria Gogou mariaangogou@gmail.com

Sleep respiratory parameters in children with idiopathic epilepsy: A cross-sectional study.

BACKGROUND The aim of this study is to explore and compare through polysomnography respiratory sleep parameters between children with idiopathic epilepsy and healthy children. METHODS Our cross-sectional study included 40 children with idiopathic epilepsy and 27 healthy children, who underwent overnight polysomnography. Data about sleep respiratory parameters were obtained and statistically analyzed. The level of statistical significance was set at 0.05. RESULTS The prevalence of Obstructive Sleep Apnea Syndrome was significantly higher in the epilepsy group (35% vs 7.4%, p<0.01). Moreover, the odds ratio of an obstructive apnea index ≥1 in the epilepsy group was 10.6 (95% Confidence Intervals: 3.08-37.08) in comparison to the control group. The mean value of the obstructive apnea-hypopnea index was significantly higher in children with epilepsy compared to healthy children (2.46±1.22 vs 1.21±0.83, p=0.027). The mean values of central apnea index and desaturation index were comparable between these two groups. Longest apnea duration was significantly higher in the group of poor seizure control. All other sleep respiratory variables did not differ significantly between children with poor and good seizure control and between children with generalized and focal epilepsy. CONCLUSIONS Children with epilepsy seem to present more prominent sleep breathing instability in comparison to healthy children, which mainly includes a predisposition to obstructive respiratory events. More studies are needed to investigate the relationship between sleep apneas and seizure control.

Cardiac manifestations in children with inborn errors of metabolism

Need and purposeCardiac involvement is a part of many inborn errors of metabolism, but has not been systematically studied. This review focuses on studies describing cardiac manifestations of inborn errors of metabolism in childhood.MethodsTwo independent reviewers searched the topic using PubMed database. Studies published within 20 years were considered, without applying any restrictions related to study design.Despite the small number of existing systematic studies on the topic, several case series/reports were identified.ConclusionsCardiomyopathy is the most frequent heart disorder in most metabolic defects. Heart rhythm disorders are mainly encountered in mitochondrial disorders and acidemias, whereas valvular dysfunction is a prominent finding in storage disorders. Cardiac involvement in mitochondrial disorders, congenital disorders of glycosylation and acidemias usually constitute an early symptom. On the contrary, in storage disorders, heart problems are revealed in later stages during routine multisystemic evaluation, with the exception of Pompe disease. As a variety of cardiac manifestations can be found in inborn errors of metabolism, these children should be systematically screened for heart problems during their follow-up.

Human herpesvirus-6 and herpes simplex virus-1 as a cause of cardiomyopathy secondary to myocarditis in children.

Kyriaki Papadopoulou-Legbelou, Maria Gogou, Paraskevi Panagopoulou, Andreas Giannopoulos and Spyridon Rammos Fourth Department of Pediatrics, Medical School, General Hospital “Papageorgiou”, Second Department of Pediatrics, Medical School, University General Hospital “AHEPA”, Aristotle University of Thessaloniki, Thessaloniki, and Department of Pediatric Cardiology, “Onassis” Cardiac Surgery Center, Athens, Greece

Sleep Disturbances in Children with Rolandic Epilepsy

Background The aim of this study is to investigate through polysomnography sleep quality in children with rolandic epilepsy and compare sleep variables between these children and healthy controls. Methods Our study population included 15 children with rolandic epilepsy and 27 healthy children who underwent overnight polysomnography. Parameters about sleep architecture and sleep respiratory events were recorded and analyzed. The level of statistical significance was set at 0.05. Results Patients and controls did not differ in basic epidemiological traits. The percentage of sleep stage rapid eye movement was significantly lower in the epilepsy group. Moreover, the mean value of the obstructive apnea index and the obstructive apnea‐hypopnea index was significantly higher in children with rolandic epilepsy compared with healthy children. Longest apnea duration and basal SpO2 during sleep had also the trend to be higher and lower, respectively, in children with epilepsy. Conclusions Children with rolandic epilepsy exhibit alterations in sleep architecture, as well as in sleep respiratory patterns. Therefore, sleep quality should be routinely considered in the long‐term follow‐up of these children.

Risk Factors for Obstructive Sleep Apnea Syndrome in Genetic Epilepsy

To the Editor: Previous studies report a high rate of Obstructive Sleep Apnea Syndrome (OSAS) in children with epilepsy and it is speculated that OSAS complicates neurocognitive outcome [1]. Moreover, surgical treatment of OSAS can contribute to reduction in seizure frequency [2]. Our aim is to investigate risk factors for OSAS in this population. We conducted a cross-sectional study approved by the Ethical Committee of the Aristotle University of Thessaloniki. In total, 40 children diagnosed with genetic epilepsy (focal or generalized) underwent clinical evaluation and overnight polysomnography. The patients with at least one seizure within the past 6 mo of polysomnography were classified as having poor seizure control (epilepsy onset-seizures recurrence). The Obstructive Apnea Index was assessed and children were divided into OSAS (14 children) and non-OSAS (26 children) groups [3]. Continuous variables were compared using t-test for independent samples and categorical using chi-square test. Mean age in the OSAS group was significantly less than in the non-OSAS group (9 .03 ± 1.64 vs . 11.37 ± 2.42; p = 0.001). Besides, in the OSAS group a significantly higher proportion of children had poor seizure control compared to the non-OSAS group (78.5 % vs. 37.5 %, p = 0.025). On the contrary, the mean value of the Body Mass Index, the female to male ratio and the prevalence of hypertrophic tonsils/ adenoids were similar between the two groups. Furthermore, epilepsy location (generalized vs. focal) and sleep-wake cycle (only nocturnal seizures vs. nocturnal and daytime seizures) do not seem to significantly affect the prevalence of OSAS (Table 1). The fact that 35 of 40 children were on one antiepileptic drug did not permit to safely investigate the impact of antiepileptic polytherapy on sleep respiratory function. OSAS in children with epilepsy is mainly driven by disease activity rather than classical anatomical factors. Epileptic seizures and residual epileptiform activity can interfere with central projections normally controlling breathing and muscle tone and disturb respiratory function during sleep. On the other hand, apneic events lead to arousals, sleep fragmentation, intermittent hypoxia * Maria Gogou mariaangogou@gmail.com