Efficacy of Melatonin as a Sleep Inducer in EEG Procedures in the Pediatric Population: A Cross-Sectional Study.

Introduction Melatonin has been used as an alternative to sleep deprivation for EEG sleep induction in the pediatric population. Our study aims to describe the efficacy of the currently used doses of melatonin for sleep induction among the pediatric age group. Methods A retrospective cross-sectional study included all patients who underwent an EEG after receiving melatonin over the period of one year. A total of 126 patients have been included in the study. Patients aged one year to three years received oral melatonin in doses between 2 mg and 6 mg. Patients in the age of three years and above received 10 mg of melatonin. Patients' success rate in achieving sleep and the exact time required for the patients to fall asleep were obtained using the readings of their EEG. The percentage of patients who have achieved sleep and the time required for those patients to sleep were calculated and correlated with the patient's gender, the presence of any associated neurobehavioral disorders, and their use of antiepileptic drugs (AED). Results Successful sleep was achieved in 84.9% (n:107) of the patients, with a mean time of 24 minutes to fall asleep (SD = 14.36). Patients with neurobehavioral disorders were 20% less likely to fall asleep when compared to other patients without neurobehavioral disorders (p: 0.003). However, there was not a statistically significant difference among different genders and among patients who received AED. Conclusion Melatonin is an effective sleep inducer for patients undergoing EEG procedures. It should be considered in the majority of patients. However, in patients with neurobehavioral disorders, a lower success rate is expected.

Phenotypic Spectrum of STXBP1 Gene Mutations in an Emirati Case Series.

Genetic mutations are increasingly recognized as etiologic factors for epilepsy and neurodevelopmental disorders. Loss of function mutations in STXBP1, one of such genes, has, in recent years, been demonstrated to cause a broad spectrum of epilepsy syndromes and chronic neurodisabilities. Syntaxin-binding protein 1 (STXBP1) is a well-recognized membrane trafficking protein responsible for synaptic transmission and is expressed ubiquitously across the brain. Our case series presents the neurodevelopmental phenotype of children with STXBP1 mutations and is the first to be reported in an Emirati patient cohort. We gathered data on five children with genetically confirmed STXBP1 mutations, each displaying varying symptomatology, EEG features, response to antiepileptic medications, and eventual disease progression. This report reveals that a majority of STXBP1 mutations were de-novo in origin; heterozygous; pathogenic to likely pathogenic variants; clinical disease onset was predominantly during infancy in the form of developmental delays with or without seizures; most of the children had co-existing ADHD or autism spectrum disorders; typical seizure semiology at onset was in the form of infantile spasms, progressing to a melange of mixed seizure types; seizure control on antiepileptic drug therapy was variable, with all cases requiring more than two medications; global developmental delay was noted in all studied children; and MRI brain findings were unremarkable in all cases. This case series demonstrates a degree of uniformity of STXBP1 mutation disease phenotypes with international literature and provides a unique insight into the genetic profile of affected children within the Emirati population.

The genomic landscape of rare disorders in the Middle East.

BACKGROUND: Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans. METHODS: We established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P < .05 was considered statistically significant. RESULTS: We present data on 1000 patients with rare diseases (46.2% females; average age, 4.6 years) representing 47 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 32.5% (95% CI, 29.7-35.5%) and was higher for genomic sequencing-based testing than chromosomal microarrays (37.9% versus 17.2%, P = 0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were encountered only once, and those with recessive inheritance accounted for ~ 62% of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7% were less than 5 years of age, and 60% were offered modified management and/or intervention plans. Interestingly, 24% of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range 7-37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-year-long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders. CONCLUSIONS: Early access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this genetically underrepresented population.

Case report: First case report of an Emirati child with a novel gene variant causing aromatic L-amino acid decarboxylase deficiency.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, neurometabolic disorder resulting from biallelic mutations in the dopa decarboxylase (DDC) gene. This is the first reported case of AADC deficiency in the United Arab Emirates (UAE) and describes an Emirati male patient who presented in the first few months of life with a severe phenotype of global hypotonia, developmental delay and oculogyric crisis. Following whole exome sequencing, a novel homozygous mutation in the DDC gene (c.1144G>T, p.Val382Phe) was reported and the patient underwent further testing, after which a diagnosis of AADC deficiency was confirmed. This mutation has not been previously described, but the clinical phenotype and corresponding biochemical profile confirmed that it is a pathogenic variant. The patient is currently managed at a tertiary referral center in the UAE and is treated in accordance with published guidance on AADC deficiency, including the recommended medical therapy combined with multidisciplinary care from a team of specialists. Some symptomatic improvements have been reported but at 5 years of age the patient continues to exhibit profound developmental delay, oculogyric crisis and is prone to recurrent respiratory infections. In order to improve outcomes for patients with AADC deficiency in the Middle Eastern region, there is an urgent need to raise the index of clinical suspicion, particularly among primary care physicians, pediatricians, and pediatric neurologists, and to improve access to diagnostic testing. This is particularly relevant at the current time, given the ongoing development of potentially disease-modifying gene therapy for AADC deficiency.

Analgesia and sedation modalities used with botulinum toxin injections in children with cerebral palsy: a literature review.

Cerebral palsy (CP) is a non-progressive motor dysfunction leading to multiple morbidities, including spasticity, which can be managed with botulinum toxin injection (BTI). This literature review aims to examine published studies on the efficacy and safety of different interventions used to reduce pain and anxiety associated with BTI in children with CP. A literature review of all published evidence in English language, or with an English translation between 1999 and 2019, using PubMed, EBSCO host, and Medline databases was carried out. All identified papers were screened for inclusion criteria. Data from included papers were entered and analyzed on an Excel database. Twenty-one studies conducted in multiple clinical settings identified 10 different analgesia and sedation modalities including intravenous ketamine, midazolam, inhaled nitrous oxide, general anesthesia, and Eutectic Mixture of Local Anesthetics (EMLA®) cream. Most of the studies were descriptive with the exception of two clinical trials and one qualitative study. All interventions had some adverse effects, but they were generally mild and no long-term sequelae were reported. The combination of inhaled nitrous oxide with EMLA® cream showed promising primary results. However, ketamine and midazolam combination could be a safe alternative. Currently, there is no sufficient data to draw on the superiority of any modality. Further high-quality studies are warranted.

Surgical Outcomes of Single-Level Bilateral Selective Dorsal Rhizotomy for Spastic Diplegia in 150 Consecutive Patients.

OBJECTIVES: Selective dorsal rhizotomy (SDR) is used to improve spasticity, gait, and pain in children with spastic diplegia. There is growing evidence supporting its long-term benefits in terms of functional outcomes, independence, and quality of life. There is, however, little contemporary work describing the surgical morbidity of this irreversible procedure. The purpose of this study is to evaluate the surgical outcomes and complications of SDR at a single United Kingdom center. METHODS: Demographics, surgical, postoperative, and follow-up data for all patients undergoing SDR between 2011 and 2016 were collected from medical records. RESULTS: Preoperative Gross Motor Function Classification System levels in 150 consecutive patients were II (35%), III (65%), and IV (1%). Median age was 6 years and 58% were male patients. There were no deaths, cerebrospinal fluid leaks, returns to theater, or readmissions within 30 days. There were no new motor or sphincter deficits. Postoperative neuropathic pain was reported by 5.3% and sensory symptoms by 8.7%. Other complications included: postoperative nausea and vomiting (19.3%), superficial wound infection (3.3%), urinary retention (1.3%), headache (6.7%), and urine or chest infection (4.7%). Follow-up data were available for all patients (93% to 12 months, 72% to 24 months). Persistent neuropathic symptoms were reported in 6.5% at 24 months. CONCLUSIONS: SDR using a single-level approach is a safe procedure with low surgical morbidity. This study complements the growing evidence base in support of SDR for spastic diplegia and should help inform decisions when considering treatment options.

Fifteen-minute consultation: when is a seizure not a seizure? Part 1, the younger child.

Paroxysmal non-epileptic events (PNEs) are common, and occur in all age groups ranging from neonates to young adults. The key to diagnosis in the majority is a detailed history and careful observation. However, a few can pose diagnostic challenges for the paediatrician to differentiate them from epileptic seizures. PNEs are usually recurrent, stereotyped and some of them tend to repeatedly occur within the same context. Although the vast majority have a benign nature, they can be a source of parental anxiety, unnecessary investigations and even potentially harmful treatments. In this review, we have described the common PNEs occurring in infants and preschool children. This will be followed by a second review for older children and adolescents. We have provided a practical diagnostic approach by dividing these events into three broad categories: PNEs associated with altered consciousness, PNEs not associated with apparently altered consciousness and sleep-related PNEs.

Fifteen-minute consultation: when is a seizure not a seizure? Part 2, the older child.

Paroxysmal non-epileptic events (PNEs) refer to episodic changes in behaviour, sensation or consciousness that lead to unusual movements, which may resemble epileptic seizures, but are not, due to excessive neuronal firing in the cerebral cortex. A significant proportion of patients seen in epilepsy clinics do not actually have epilepsy. Therefore, it is paramount for clinicians to be able to recognise these transient non-epileptic events in order to avoid unnecessary antiepileptic treatments and to provide appropriate management as required. These PNEs can be observed within the context of a neurological disorder such as migraine or with no direct neurological basis such as simple tics. In this review, we have described common PNEs presenting in school-age children and adolescents alongside the clinical approach to differentiate them from epileptic seizures. PNEs occurring in infancy and younger children have been covered in our first review of this series.

How to use lumbar puncture in children.

Lumbar puncture (LP) is a useful diagnostic tool in a wide spectrum of paediatric clinical situations. A common indication is to rule out a serious intracranial infection in a febrile child. Success rate can be optimised by proper positioning, appropriate technique and enhanced operator's skill in performing the procedure. The purpose of this review is to explore the indications and contraindications for performing paediatric LP, to describe the anatomical and physiological knowledge required to maximise success rates and to describe complications and their management. We will also provide advice on requesting various cerebrospinal fluid studies, interpretation of results and clinical situations in which LP may be indicated.

Narcolepsy in children: a diagnostic and management approach.

OBJECTIVE: To provide a diagnostic and management approach for narcolepsy in children. METHODS: Narcolepsy is a chronic disabling disorder characterized by excessive daytime sleepiness, cataplexy, hypnogogic and/or hypnopompic hallucinations, and sleep paralysis. All four features are present in only half of the cases. Excessive daytime sleepiness is the essential feature of narcolepsy at any age and is usually the first symptom to manifest. A combination of excessive daytime sleepiness and definite cataplexy is considered pathognomonic of narcolepsy syndrome. RESULTS: New treatment options have become available over the past few years. Early diagnosis and management can significantly improve the quality of life of patients with narcolepsy with cataplexy. CONCLUSION: This review summarizes the pathophysiology, clinical features, and management options for children with narcolepsy.

Fifteen-minute consultation: the child with idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a rare condition where intracranial hypertension is found in the context of normal brain parenchyma and no mass lesion, ventriculomegaly, underlying infection, or malignancy. Our understanding of this condition has greatly improved in the recent years with neuroimaging features and normal values for lumbar puncture opening pressure now well defined. This article provides a review of IIH in children and revised diagnostic criteria based on recent evidence and published opinion. We have also presented an algorithmic approach to the child with possible IIH.