"Atypical forms" of benign epilepsy with centrotemporal spikes (BECTS): How to diagnose and guide these children. A practical/scientific approach.

Benign epilepsy with centrotemporal spikes (BECTS) epilepsy, also known as rolandic epilepsy, is the most common childhood type of epilepsy. There is debate on its "benign" definition given the numerous literature data on its correlation to cognitive morbidity. Although its prognosis is often favorable, BECTS can present or evolve however to an atypical form, characterized by a worse prognosis and negative impact on cognitive development. It is possible that abnormal electrical activity, marker of neurological dysfunction, has the potential to disrupt neural network function and development. Numerous studies tried to identify clinical or electroencephalographic criteria for atypical forms and atypical evolution of BECTS in order to guide follow-up and treatment of patients and to predict their outcome. This review provides a compact summery of literature data with a focus on predictive features of future cognitive decline.

Vertigo/dizziness in pediatric emergency department: Five years' experience.

BACKGROUND: Vertigo/Dizziness in childhood is not a rare cause of visits to the emergency department (ED). We analyzed a selected group with vertigo/dizziness to identify signs and symptoms that may help to guide the diagnostic approach and management. METHODS: A total of 616 children admitted for vertigo to the ED over a five-year period were retrospectively reviewed. Their medical history, clinical characteristics, laboratory and neuroimaging tests, final diagnoses and management were analyzed. RESULTS: Migraine and syncope were the most frequent causes. Two patients were affected by life-threatening cardiac syncope, while structural life-threatening central nervous system diseases were found in 15 patients, none of whom presented with vertigo as an isolated clinical finding. CONCLUSIONS: Most cases of vertigo/dizziness in childhood that consist mainly of migraine and syncope are of benign origin. The prompt identification of neurological or cardiological signs or symptoms associated with vertigo in children is mandatory to rule out life-threatening conditions.

Headache and ADHD in Pediatric Age: Possible Physiopathological Links.

Primary headache and attention-deficit/hyperactivity disorder (ADHD) are common disorders in children and adolescences, frequently associated to severe cognitive, emotional, and behavioral impairments. They both are a disabling condition with consequences on family and child's quality of life. Literature data on their association are contrasting. Dopaminergic system dysfunction, brain iron deficiency, and sleep disturbance should be considered to better understand headache and ADHD overlap. In this review, we analyze the complex association between these two diseases and the potential impact on child neurodevelopment.

Headache and attention deficit and hyperactivity disorder in children: common condition with complex relation and disabling consequences.

The aim of this review was to analyze literature data on the complex association between headache and attention deficit and hyperactivity disorder (ADHD) in children, in order to explore its possible consequences on child neurological development. Headache and ADHD are two common conditions in the pediatric population. They both are disabling diseases that impact the child's quality of life and are associated with severe cognitive, emotional, and behavioral impairments. To assess and analyze literature data about the association of ADHD and headache in children and possible physiopathogenesis relationships, we searched for the following terms: headache, migraine, tension-type headache, ADHD, and children (MESH or text words). We found different studies that assess the clinical, epidemiological, and physiopathogenetic overlap between these two diseases, with contrasting results and unresolved questions. Structural and functional abnormalities in brain networks have been found to be central in both headache and ADHD pathophysiology. It will be crucial to gain a better understanding of how subcortical-cortical and corticocortical network development is altered during the onset of the disorders.

Gastroesophageal reflux disease vs. Panayiotopoulos syndrome: an underestimated misdiagnosis in pediatric age?

Autonomic signs and symptoms could be of epileptic or nonepileptic origin, and the differential diagnosis depends on a number of factors which include the nature of the autonomic manifestations themselves, the occurrence of other nonictal autonomic signs/symptoms, and the age of the patient. Here, we describe twelve children (aged from ten months to six years at the onset of the symptoms) with Panayiotopoulos syndrome misdiagnosed as gastroesophageal reflux disease. Gastroesophageal reflux disease and Panayiotopoulos syndrome may represent an underestimated diagnostic challenge. When the signs/symptoms occur mainly during sleep, a sleep EEG or, if available, a polysomnographic evaluation may be the most useful investigation to make a differential diagnosis between autonomic epileptic and nonepileptic disorders. An early detection can reduce both the high morbidity related to mismanagement and the high costs to the national health service related to the incorrect diagnostic and therapeutic approaches. To decide if antiseizure therapy is required, one should take into account both the frequency and severity of epileptic seizures and the tendency to have potentially lethal autonomic cardiorespiratory involvement. In conclusion, we would emphasize the need to make a differential diagnosis between gastroesophageal reflux disease and Panayiotopoulos syndrome in patients with "an unusual" late-onset picture of GERD and acid therapy-resistant gastroesophageal reflux, especially if associated with other autonomic symptoms and signs.

Adenotonsillectomy and orthodontic therapy in pediatric obstructive sleep apnea.

PURPOSE: Rapid maxillary expansion (RME) is an additional treatment in pediatric obstructive sleep apnea (OSA). The aim of this study was to present data about the outcome of adenotonsillectomy (AT) and of RME in a clinical sample of pediatric OSA. METHODS: We consecutively enrolled children with OSA to undergo RME or AT. The age and the severity of OSA are the main factors involved in the choice of treatment. A polysomnography was performed at the baseline (i.e., before treatment, T0) and 1 year after treatment (T1). RESULTS: A total of 52 subjects fulfilled the inclusion criteria. Twenty-five children underwent AT (group 1) and 22 children underwent RME (group 2). Five children underwent both treatments (group 3). Children in group 2 were older, had a longer disease duration, a higher body mass index (BMI), a lower apnea-hypopnea index (AHI), and a lower arousal index at T0 than children in group 1. After 1 year, BMI percentile and overnight mean saturation increased in group 1 while AHI and arousal index decreased. In group 2, mean overnight saturation increased while AHI decreased. Children in group 3 displayed a significant decrease in AHI from T0 to T1. CONCLUSIONS: Our data demonstrate that both treatments help to improve OSA, and a multidisciplinary approach to treatment is suggested.

Sleep clinical record: an aid to rapid and accurate diagnosis of paediatric sleep disordered breathing.

Overnight polysomnography (PSG) is an expensive procedure which can only be used in a minority of cases, although it remains the gold standard for the diagnosis of sleep disordered breathing (SDB). The objective of this study was to develop a simple, PSG-validated tool to screen SDB, thus reducing the use of PSG. For every participant we performed PSG and a sleep clinical record was completed. The sleep clinical record consists of three items: physical examination, subjective symptoms and clinical history. The clinical history analyses behavioural and cognitive problems. All three items were used to create a sleep clinical score (SCS). We studied 279 children, mean ± SD age 6.1 ± 3.1 years, 63.8% male; 27.2% with primary snoring and 72.8% with obstructive sleep apnoea (OSA) syndrome. The SCS was higher in the OSA syndrome group compared to the primary snoring group (8.1 ± 9.6 versus 0.4 ± 0.3, p<0.005), correlated with apnoea/hypopnoea index (p=0.001) and had a sensitivity of 96.05%. Positive and negative likelihood ratios were 2.91 and 0.06, respectively. SCS may effectively be used to screen patients as candidates for PSG study for suspected OSA syndrome, and to enable those with a mild form of SDB to receive early treatment.

Neonatal Cerebral Venous Thrombosis following Maternal SARS-CoV-2 Infection in Pregnancy.

A possible consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the development of an exacerbated thrombophilic status, and cerebral venous thrombosis (CVT) is a rare but possible complication of SARS-CoV-2 infection reported both in adults and in children. The present case report describes the clinical course of a term neonate showing extended CVT of unclear origin, whose mother had developed SARS-CoV-2 infection during the third trimester of pregnancy. We speculate that the prothrombotic status induced by maternal SARS-CoV-2 infection may have played a pathophysiological role in the development of such severe neonatal complication. Further investigations are required to confirm such hypothesis.

Autonomic cardiovascular tests in children with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: The aim of our study was to investigate cardiovascular autonomic activity during wakefulness, using cardiovascular tests, in a population of children with OSAS. DESIGN: Prospective study. SETTING: Sleep unit of an academic center. PARTICIPANTS: We included 25 children (mean age 10.2 +/- 2.3 years) undergoing a diagnostic assessment for OSAS, and 25 age-matched healthy control subjects. All subjects underwent an overnight polysomnography and autonomic cardiovascular tests using parts of the Ewing test battery, which is a physiological test used for the assessment of autonomic function (head-up tilt test, Valsalva maneuver, deep breathing test). MEASUREMENTS AND RESULTS: Eighteen of 25 children with OSAS (11 males, mean age 9.4 +/- 1.7 years) concluded the study. OSAS patients had higher systolic blood pressure, diastolic blood pressure, baseline heart rate, the 30:15 index (which represents the RR interval at the 15th and 30th beats during the head up tilt test), and delta diastolic and systolic blood pressure during the head-up tilt test, while the heart rate variability during the deep breathing test was lower, compared with controls. A positive correlation between systolic and diastolic blood pressure and the apnea-hypopnea index (AHI), and negative between AHI and both the 30:15 index and Valsalva ratio, were found. Stepwise linear regression analysis detected a negative correlation between AHI and the 30:15 index and Valsalva ratio, a positive correlation between overnight mean oxygen saturation and delta heart rate, and between AHI and delta systolic blood pressure. CONCLUSIONS: Our data point to an increase in basal sympathetic activity during wakefulness and to an impaired reaction to several physiological stimuli, which is dependent on the severity of OSAS.

Cognitive profile, parental education and BMI in children: reflections on common neuroendrocrinobiological roots.

Overweight and obesity may be associated with cognitive problems and both may share "neuroendocrinobiological roots" in common cerebral areas. We investigated intellectual performances and a possible "specific cognitive profile" in overweight/obese children. A cross-sectional study was conducted on 898 school children (6 to 13 years) attending primary schools. Wechsler Intelligence Scale for Children-revised (WISC-R) revealed significant differences in performance intelligence quotient (PIQ) scores between body mass index (BMI) subgroups (p < 0.01). Regression analysis identified BMI as the only variable significantly related to PIQ (p < 0.05). Gender (p < 0.05) and parental educational score (p < 0.001) were significantly related to verbal intelligence quotient (VIQ). Parental educational score was the only factor significantly related to total intelligence quotient (TIQ) (p < 0.05). Parental education seems to play a major role in TIQ and VIQ; a lower PIQ score is clearly related to a higher BMI. A routine neurocognitive assessment in overweight/obese children is recommended. Finally, we have added some reflections on common neuroendocrinobiological roots.

Headache and cognitive profile in children: a cross-sectional controlled study.

We investigated whether children affected by tension-type headache and migraine without aura, compared with a healthy control group that was matched by age, culturally and socioeconomically display a diverse intellectual functioning and have a separate "cognitive profile". A cross-sectional study was conducted from January 2006 to November 2008 at "Sapienza University" in Rome. A total of 134 children were diagnosed as being affected by either migraine without aura (93) or tension-type headache (41). On the basis of our exclusion/inclusion criteria, we enrolled 82 of these 134 children, 63 of whom were affected by migraine without aura and 19 by tension-type headache. On entry, cognitive functions were assessed in both the affected subjects and the control group by the Wechsler Intelligence Scale for Children-revised. Significant differences were found between the headache and control groups in the mean total intelligence quotient and verbal intelligence quotient scores (p < 0.001). Significant negative correlations were found between the total intelligence quotient, verbal intelligence quotient, performance intelligence quotient and the frequency of attacks (r = -0.55 and p < 0.001, r = -0.61 and p < 0.001, r = -0.29 and p < 0.01, respectively), as well as between the total intelligence quotient score and the age at headache onset (r = 0.234, p < 0.05). Our results suggest that the cognitive profile of children affected by headache should be assessed at the first child neurology outpatient observation. From a therapeutic point of view, although within a normal range, the abilities most likely to be less brilliant in such children are verbal skills.

Migraine treatment in developmental age: guidelines update.

There is a serious lack of controlled studies on the pharmacological treatment of primary migraine in the developmental age; there is, consequently, an urgent need for new, evidence-based approaches to this long-neglected field of research. Moreover, previous studies have stated that the placebo response is greater in pediatric patients than in adults and that a reduction in the attack frequency in the absence of any pharmacological treatment is observed more frequently in pediatric migraine patients than in adults. Besides these preliminary considerations, the shorter duration of migraine attacks and other characteristic semeiological features of the clinical picture in children are such that the design of randomized controlled trial (RCT) is more problematic in the developmental age than in the adult. Bearing in mind all these weak points, the aim of this review was to summarize and update recent guidelines for the treatment of primary migraine in children and adolescents. The most recent guidelines are those published by the Italian Society for the study of Headache, the French Society for the study of Migraine and Headache, and the American Academy of Neurology. We have incorporated into these guidelines the results from the few, recent RCTs, clinical controlled trials, open-label studies, meta-analyses and reviews that have been published since 2004; owing to the lack of strong evidence in this field of research, we have sometimes even mentioned pilot non-controlled studies, case series and expert opinions. Lastly, evidence was classified and the recommendations were categorized according to different levels.

[Parenteral nutrition with preconceived bag in a preterm newborn ELBW.] / Nutrizione parenterale con sacca precostituita in un neonato pretermine di peso estremamente basso.

INTRODUCTION: The administration of adequate nutritional intake, from the first days of life, is of fundamental importance in the management of the newborn extremely low birth weight (ELBW): parenteral nutrition (PN), as a support for early enteral feeding, plays a central role in the attempt to guarantee a quantitative and qualitative growth similar to that of the fetus in utero, allowing an adequate caloric, macro and micronutrient intake. The standardized PN, carried out through pre-established bags, allows in the case in which is not possible a personalized preparation, balanced nutritional contributions, reducing the risk of microbiological contamination and errors in preparation. CLINICAL CASE: We describe the case of an extremely preterm infant with various co-morbid conditions (severe respiratory syndrome, cerebral hemorrhage, anemia, sepsis and patency of the arterial duct) in which PN was used in a pre-established bag, as a support to enteral feeding in the first weeks of life, characterized by extreme clinical instability. CONCLUSIONS: PN is essential for some types of newborns and in particular for the ELBW preterms in which enteral feeding, although undertaken early, does not guarantee the necessary contributions to promote adequate growth. The use of NP in a pre-made bag can be a valid alternative to individualized formulations, where not available.

Cannabidiol Treatment for Refractory Epilepsies in Pediatrics.

Cannabis extracts in oil are becoming increasingly available, and, during the last years, there has been growing public and scientific interest about therapeutic properties of these compounds for the treatment of several neurologic diseases, not just epilepsy. The discovered role of the endocannabinoid system in epileptogenesis has provided the basis to investigate the pharmacological use of exogenously produced cannabinoids, to treat epilepsy. Although, physicians show reluctance to recommend Cannabis extracts given the lack of high-quality safety available data, from literature data cannabidiol (CBD) results to be a promising and safe anticonvulsant drug with low side-effect. In particular, according to early studies, CBD can reduce the frequency of seizures and lead to improvements in quality of life in children affected by refractory epilepsy. So, for these reasons, the detailed study of the interactions between CBD and anticonvulsant drugs (AEDs) administered simultaneously in polytherapy, is arousing increasing interest, to clarify and to assess the incidence of adverse effects and the relation between dose escalation and quality of life measures. To date, in pediatric age, CBD efficacy and safety is not supported by well-designed trials and strong scientific evidence are not available. These studies are either retrospective or small-scale observational and only during the last years Class I evidence data for a pure form of CBD have been available, as demonstrated in placebo-controlled RCTs for patients affected by Lennox-Gastaut syndrome and Dravet syndrome. It is necessary to investigate CBD safety, pharmacokinetics and interaction with other AEDs alongside performing double-blinded placebo-controlled trials to obtain conclusive data on its efficacy and safety in the most frequent epilepsies in children, not just in the epileptic encephalopathy. This review was aimed to revise the available data to describe the scientific evidence for CBD in Pediatric Epilepsies.

Prevalence of EEG paroxysmal activity in a population of children with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Sleep breathing disorders may trigger paroxysmal events during sleep such as parasomnias and may exacerbate preexisting seizures. We verified the hypothesis that the amount of EEG paroxysmal activity (PA) may be high in children with obstructive sleep apnea syndrome (OSAS). DESIGN: Prospective study. SETTINGS: Sleep unit of an academic center. PARTICIPANTS: Polysomnographic studies were performed in a population of children recruited prospectively, for suspected OSAS, from January to December 2007, with no previous history of epileptic seizures or any other medical conditions. All sleep studies included > or = 8 EEG channels, including centrotemporal leads. We collected data about clinical and respiratory parameters of children with OSAS and with primary snoring, then we performed sleep microstructure analysis in 2 OSAS subgroups, matched for age and sex, with and without paroxysmal activity. MEASUREMENTS AND RESULTS: We found 40 children who met the criteria for primary snoring, none of them showed PA, while 127 children met the criteria for OSAS and 18 of them (14.2%) showed PA. Children with PA were older, had a predominance of boys, a longer duration of OSAS, and a lower percentage of adenotonsillar hypertrophy than children without PA. Moreover, PA occurred over the centrotemporal regions in 9 cases, over temporal-occipital regions in 5, and over frontocentral regions in 4. Children with PA showed a lower percentage of REM sleep, a lower CAP rate and lower A1 index during slow wave sleep, and lower total A2 and arousal index than children without EEG abnormalities. CONCLUSIONS: We found a higher percentage of paroxysmal activity in children with OSAS, compared to children with primary snoring, who did not exhibit EEG abnormalities. The children with paroxysmal activity have peculiar clinical and sleep microstructure characteristics that may have implications in the neurocognitive outcome of OSAS.

Ictal Epileptic Headache: When Terminology Is Not a Moot Question.

The relationship between headache and epilepsy is complex and despite the nature of this association is not yet clear. In the last few years, it has been progressively introduced the concept of the "ictal epileptic headache" that was included in the recently revised International Classification of Headaches Disorders 3rd edition (ICHD-3-revised). The diagnostic criteria for ictal epileptic headache (IEH) suggested in 2012 were quite restrictive thus leading to the underestimation of this phenomenon. However, these criteria have not yet been included into the ICHD-3 revision published in 2018, thus creating confusion among both, physicians and experts in this field. Here, we highlight the importance to strictly apply the original IEH criteria explaining the reasons through the analysis of the clinical, historical, epidemiological and pathophysiological characteristics of the IEH itself. In addition, we discuss the issues related to the neurophysiopathological link between headache and epilepsy as well as to the classification of these epileptic events as "autonomic seizure."

Management of Childhood Headache in the Emergency Department. Review of the Literature.

Headache is the third cause of visits to pediatric emergency departments (ED). According to a systematic review, headaches in children evaluated in the ED are primarily due to benign conditions that tend to be self-limiting or resolve with appropriate pharmacological treatment. The more frequent causes of non-traumatic headache in the ED include primitive headaches (21.8-66.3%) and benign secondary headaches (35.4-63.2%), whereas potentially life-threatening (LT) secondary headaches are less frequent (2-15.3%). Worrying conditions include brain tumors, central nervous system infections, dysfunction of ventriculo-peritoneal shunts, hydrocephalus, idiopathic intracranial hypertension, and intracranial hemorrhage. In the emergency setting, the main goal is to intercept potentially LT conditions that require immediate medical attention. The initial assessment begins with an in-depth, appropriate history followed by a complete, oriented physical and neurological examination. The literature describes the following red flags requiring further investigation (for example neuroimaging) for recognition of LT conditions: abnormal neurological examination; atypical presentation of headaches: subjective vertigo, intractable vomiting or headaches that wake the child from sleep; recent and progressive severe headache (<6 months); age of the child <6 years; no family history for migraine or primary headache; occipital headache; change of headache; new headache in an immunocompromised child; first or worst headache; symptoms and signs of systemic disease; headaches associated with changes in mental status or focal neurological disorders. In evaluating a child or adolescent who is being treated for headache, physicians should consider using appropriate diagnostic tests. Diagnostic tests are varied, and include routine laboratory analysis, cerebral spinal fluid examination, electroencephalography, and computerized tomography or magnetic resonance neuroimaging. The management of headache in the ED depends on the patient's general conditions and the presumable cause of the headache. There are few randomized, controlled trials on pharmacological treatment of headache in the pediatric population. Only ibuprofen and sumatriptan are significantly more effective than placebo in determining headache relief.

Clinical reappraisal of the influence of drug-transporter polymorphisms in epilepsy.

INTRODUCTION: Although novel antiepileptic drugs (AEDs) have been recently released, the issue of drug resistance in epileptic patients remains unsolved and largely unpredictable. Areas covered: We aim to assess the clinical impact of genetic variations that may influence the efficacy of medical treatment in epilepsy patients. Indeed, many genes, including genes encoding drug transporters (ABCB1), drug targets (SCN1A), drug-metabolizing enzymes (CYP2C9, CYP2C19), and human leucocyte antigen (HLA) proteins, may regulate the mechanisms of drug resistance in epilepsy. This review specifically focuses on the ABC genes, which encode multidrug resistance-associated proteins (MRPs) and may reduce the blood-brain barrier penetration of anticonvulsant AEDs. Expert opinion: Drug resistance remains a crucial problem in epilepsy patients. Pharmacogenomic studies may improve our understanding of drug responses and drug resistance by exploring the impact of gene variants and predicting drug responses and tolerability.

Pharmacological considerations in the use of stiripentol for the treatment of epilepsy.

INTRODUCTION: Despite the fact that more than 20 antiepileptic drugs (AEDs) are currently available, about one-third of patients still present drug resistance. Further efforts are required to develop novel and more efficacious therapeutic strategies, especially for refractory epileptic syndromes showing few and anecdotic therapeutic options. AREAS COVERED: Stiripentol (STP) is a second generation AED that shows GABAergic activity, with immature brain selectivity, and an indirect metabolic action on co-administered AEDs. Two pivotal studies demonstrated STP efficacy in patients with Dravet syndrome with refractory partial seizures, and marketing authorization in Europe, Canada and Japan was granted thereafter. Post-marketing surveys reported a good efficacy and tolerability profile. In addition, interesting data is currently emerging regarding off-label experimentation of STP in other forms of epilepsy. EXPERT OPINION: STP is an important addition to the limited treatment options available for patients resistant to common AEDs. The possibility to inhibit seizures through the metabolic pathway of lactate dehydrogenase and the inhibitory effects on the entry of Na(+) and Ca(2+) are the most recent findings to emerge about STP and could be proof of its neuroprotective action. Moreover, its positive effects on cognitive function, its good safety and tolerability profile and the increasing data about STP efficacy on other refractory epileptic syndromes may prove to be fertile grounds for further investigation.

Cannabidiol as potential treatment in refractory pediatric epilepsy.

In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children. From in vitro and in vivo studies on animal models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a favorable side-effect profile. In humans, CBD efficacy and safety is not supported by well-designed trials and its use has been described by anecdotal reports. It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other anti-epileptic drugs (AEDs) alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.