Sleep in Children with Congenital Malformations of the Central Nervous System.

PURPOSE OF REVIEW: Congenital malformations of the central nervous system may be seen in isolation or in association with syndromes that have multiorgan involvement. Among the potential health challenges these children may face, sleep concerns are frequent and may include chronic insomnia, sleep-related breathing disorders, and circadian rhythm disorders. RECENT FINDINGS: In this review, we describe recent research into sleep disorders affecting children with congenital malformations of the CNS including visual impairment, septo-optic dysplasia, agenesis of the corpus callosum, Aicardi syndrome, Chiari malformation, spina bifida, achondroplasia, Joubert syndrome, fetal alcohol spectrum disorders, and congenital Zika syndrome. In many cases, the sleep disturbance can be directly related to observed anatomical differences in the brain (such as in apnea due to Chiari malformation), but in most syndromes, a complete understanding of the underlying pathophysiology connecting the malformation with sleep problem is still being elucidated. Our review provides a synthesis of available evidence for clinicians who treat this patient population, in whom appropriate diagnosis and management of sleep problems may improve the quality of life for both patient and caregiver.

Utility and safety of prolonged video-EEG monitoring in a tertiary pediatric epilepsy monitoring unit.

Prolonged video-EEG (vEEG) monitoring helps characterize paroxysmal events and epilepsy. There is limited literature in pediatrics describing the safety and utility of vEEG. We retrospectively reviewed 454 pediatric epilepsy monitoring unit admissions over two years. Final event diagnoses, duration of seizures, and medical complications were analyzed. Two hundred twenty admissions (48.4%) captured epileptic seizures, 150 (33.0%) captured nonepileptic events, and 84 (18.5%) failed to capture any events. Medical complications were seen in 4 patients (1.8%) with no long-term complications. Seventeen episodes of status epilepticus occurred in 13 patients. This constituted 2.9% of all admissions and 5.9% of admissions with epileptic seizures. The median duration of status was 26 min, and three patients required transfer to the pediatric intensive care unit. Video-EEG monitoring had a high yield in capturing events and differentiating epileptic from nonepileptic events. Our pediatric patients experienced greater risk of status epilepticus but lesser risk of injury.

Sleep Disorders and Chronic Pain Syndromes in the Pediatric Population.

Sleep problems are widespread in children and adolescents suffering from chronic pain disorders. Sleep loss intensifies the experience of pain and is detrimental to the budding self-efficacy of a young individual with limitless horizons. Addressing sleep disorders may prevent the chronification of pain and prevent adverse health outcomes, such as functional impairment, psychiatric comorbidities and overall poor quality of life. This review will explore the cyclical nature between sleep, pain and mood, as well as the functional impact of this relationship on children and adolescents. There will be a discussion about sleep assessment and diagnostic testing, followed by a description of sleep disturbances found in specific pain conditions, ranging from headache, musculoskeletal/abdominal pain, to rheumatologic disorders. Finally, there will be a brief review of pharmacologic and behavioral interventions designed to improve sleep quality, and when possible, to alleviate pain.

Telemedicine-based sleep services for a complex child: optimizing care during a pandemic and beyond.

A 12-year-old male with nonverbal autism and morbid obesity was referred to a pediatric sleep center during the SARS-CoV-2 pandemic for complaints of snoring with tonsillar hypertrophy and difficulty falling asleep. Due to social challenges, the family had not sought in-person care in the past. Through telemedicine consultation and home sleep apnea testing, the patient was diagnosed with obstructive sleep apnea as well as an irregular sleep-wake disorder. This unique utilization of the health care system in the care of a complex patient with multiple sleep disorders demonstrates the utility of remote care and testing. There is a great benefit to continuing to provide pediatric sleep care in this way beyond the pandemic.

EEG and video-EEG seizure monitoring has limited utility in patients with hypothalamic hamartoma and epilepsy.

PURPOSE: Hypothalamic hamartomas (HHs) are a malformation of the ventral hypothalamus and tuber cinereum, associated with gelastic seizures and epilepsy. We sought to determine the spectrum of electroencephalography (EEG) abnormalities in a large cohort of HH patients. METHODS: Data was collected for HH patients undergoing evaluation between 2003 and 2007. Data included seizure history, prior treatment, and results of diagnostic studies. After informed consent, data were entered into a database. KEY FINDINGS: We reviewed 133 HH patients. Mean age at time of data analysis was 15.7 years (59.4% male). Most patients had gelastic (77%) and/or complex partial seizures (58%). Records for 102 EEG studies on 73 patients were reviewed. Interictal epileptiform abnormalities were seen in 77%, localizing predominately to the temporal and frontal regions. Records for 104 video-EEG (VEEG) studies on 65 patients were reviewed. Of 584 gelastic seizures (GS) captured, no ictal EEG change was noted in 438 (75%). Of GS with localizing features, 89% suggested onset from the temporal and/or frontal regions. There were 160 complex partial seizures (CPS). For those with localizing features, 100% localized to the temporal and/or frontal head regions. EEG and VEEG findings correlated with the side of HH attachment. VEEG did not influence outcome. SIGNIFICANCE: EEG features in HH patients are diverse. The majority of gelastic seizures fail to demonstrate change in the EEG. The lack of EEG changes with many clinical seizures, and the false localization seen in those events with an ictal change suggest the utility of EEG is limited in the evaluation of these patients.

Clinical features of paediatric and adult autoimmune encephalitis: A multicenter sample.

BACKGROUND: Autoimmune encephalitis (AE) is a heterogeneous class of inflammatory diseases of the brain that can present with a wide spectrum of neuropsychiatric symptoms. Patients may be negative for CSF anti-neuronal antibodies, which can make the diagnosis of AE challenging. Distinguishing features between paediatric and adult patients with AE are not well characterized. OBJECTIVE: Describe the clinical presentation, seizure type, EEG and sleep patterns in paediatric and adult patients with AE. METHODS/DESIGN: Retrospective review of clinical data from paediatric and adult patients diagnosed with AE from three medical centers between 1/2008-12/2019. RESULTS: We included 100 patients with AE, including 65 children. Median age at presentation was 14 years (1-88years). Fifty-five patients had positive CSF autoantibody results (NMDAR 36%, VGKC Ab 10%, anti-GAD65 4%, miscellaneous 3%), and 47 patients were autoantibody-negative. Paediatric patients were more likely to present with psychiatric symptoms, focal seizures and/or status epilepticus, and sleep disturbances compared to adult patients (p < 0.05). There was a higher incidence of NMDA-R encephalitis in children compared to adults. CONCLUSION: Paediatric patients with AE were more likely to present with psychiatric symptoms, sleep disturbances, focal seizures, and/or status epilepticus compared to adults (p < 0.05). Insomnia and hypersomnia are common sleep problems associated with AE that should be screened early in the diagnostic evaluation. Further studies can be performed to explore the relationship between sleep disturbances and long-term cognitive effects and the incidence of chronic epilepsy in this subset of patients.

The use of telemedicine for the diagnosis and treatment of sleep disorders: an American Academy of Sleep Medicine update.

NONE: The COVID-19 pandemic led to widespread use of telemedicine and highlighted its importance in improving access to sleep care and advocating for sleep health. This update incorporates the lessons learned from such widespread utilization of telehealth to build on the American Academy of Sleep Medicine's 2015 position paper on the use of telemedicine for diagnosing and treating sleep disorders. Important key factors in this update include an emphasis on quality and value, privacy and safety, health advocacy through sleep telemedicine, and future directions.

Resting-state functional MRI connectivity impact on epilepsy surgery plan and surgical candidacy: prospective clinical work.

OBJECTIVE: The authors' goal was to prospectively quantify the impact of resting-state functional MRI (rs-fMRI) on pediatric epilepsy surgery planning. METHODS: Fifty-one consecutive patients (3 months to 20 years old) with intractable epilepsy underwent rs-fMRI for presurgical evaluation. The team reviewed the following available diagnostic data: video-electroencephalography (n = 51), structural MRI (n = 51), FDG-PET (n = 42), magnetoencephalography (n = 5), and neuropsychological testing (n = 51) results to formulate an initial surgery plan blinded to the rs-fMRI findings. Subsequent to this discussion, the connectivity results were revealed and final recommendations were established. Changes between pre- and post-rs-fMRI treatment plans were determined, and changes in surgery recommendation were compared using McNemar's test. RESULTS: Resting-state fMRI was successfully performed in 50 (98%) of 51 cases and changed the seizure onset zone localization in 44 (88%) of 50 patients. The connectivity results prompted 6 additional studies, eliminated the ordering of 11 further diagnostic studies, and changed the intracranial monitoring plan in 10 cases. The connectivity results significantly altered surgery planning with the addition of 13 surgeries, but it did not eliminate planned surgeries (p = 0.003). Among the 38 epilepsy surgeries performed, the final surgical approach changed due to rs-fMRI findings in 22 cases (58%), including 8 (28%) of 29 in which extraoperative direct electrical stimulation mapping was averted. CONCLUSIONS: This study demonstrates the impact of rs-fMRI connectivity results on the decision-making for pediatric epilepsy surgery by providing new information about the location of eloquent cortex and the seizure onset zone. Additionally, connectivity results may increase the proportion of patients considered eligible for surgery while optimizing the need for further testing.

A novel mutation of the ARX gene in a male with nonsyndromic mental retardation.

ARX (Aristaless-related homeobox gene) is located at Xp22. It contains 5 exons and encodes a 562-amino acid protein. The protein contains 4 polyalanine tracts, 3 of which are encoded in exon 2 and 1 in exon 4. Mutations in the ARX gene have been found in X-linked infantile spasms syndrome, Partington syndrome (mental retardation with dystonic movements of the hands), X-linked lissencephaly with abnormal genitalia, X-linked myoclonus epilepsy with spasticity and intellectual disability, and in nonsyndromic X-linked mental retardation. The most common mutation in ARX (seen in X-linked infantile spasms syndrome, Partington syndrome, and X-linked mental retardation) is a 24-bp duplication in exon 2 resulting in expansion of a polyalanine tract. Truncating mutations (deletions, frameshift, non-sense) have been found in X-linked lissencephaly with abnormal genitalia, as well as homeodomain missense mutations in X-linked myoclonus epilepsy with spasticity and intellectual disability. The authors report a novel 24-bp in-frame deletion within exon 2 of the ARX gene in a male child with X-linked mental retardation and review the spectrum of ARX mutations. This mutation results in a contraction of the second polyalanine repeat.

Benign afebrile seizures in acute gastroenteritis: is rotavirus the culprit?

Three patients, a 2-year-old girl, a 14-month-old girl, and a 15-month-old boy, were admitted with multiple episodes of benign afebrile seizures. Electroencephalograms recorded 1 or 2 days after the last seizure revealed epileptiform discharges. All 3 patients developed a fulminant Rotazyme-positive diarrhea toward the end of their respective hospital stay. The prospects of immunological detection in diagnosis and treatment are discussed.

Electroclinical phenotypes and outcomes in TBC1D24-related epilepsy.

TBC1D24 is a newly recognized gene in which variations lead to variable clinical phenotypes including drug-resistant epilepsy. We report four patients with novel variants of TBC1D24 demonstrating drug-resistant focal epilepsy, developmental delays, and head growth deceleration. All patients had seizure semiologies consisting of prolonged, unilateral, focal clonic activity of the arm, leg or face, in addition to generalized clonic or myoclonic seizures. Ictal EEG characteristics included epilepsia partialis continua, epilepsy of infancy with migrating focal seizures, and other focal seizures with indiscrete interictal-ictal transitions. Two seemingly unrelated Navajo patients with identical variations experienced super-refractory status epilepticus at 9 months of age, with one achieving resolution with ketogenic diet therapy. Our series suggests that TBC1D24-related epilepsy can manifest with hypotonia, developmental delays, and a variety of focal-onset seizures prone to electroclinical dissociation.

Recommended Amount of Sleep for Pediatric Populations: A Consensus Statement of the American Academy of Sleep Medicine.

ABSTRACT: Sleep is essential for optimal health in children and adolescents. Members of the American Academy of Sleep Medicine developed consensus recommendations for the amount of sleep needed to promote optimal health in children and adolescents using a modified RAND Appropriateness Method. The recommendations are summarized here. A manuscript detailing the conference proceedings and the evidence supporting these recommendations will be published in the Journal of Clinical Sleep Medicine.

Consensus Statement of the American Academy of Sleep Medicine on the Recommended Amount of Sleep for Healthy Children: Methodology and Discussion.

ABSTRACT: Members of the American Academy of Sleep Medicine developed consensus recommendations for the amount of sleep needed to promote optimal health in children and adolescents using a modified RAND Appropriateness Method. After review of 864 published articles, the following sleep durations are recommended: Infants 4 months to 12 months should sleep 12 to 16 hours per 24 hours (including naps) on a regular basis to promote optimal health. Children 1 to 2 years of age should sleep 11 to 14 hours per 24 hours (including naps) on a regular basis to promote optimal health. Children 3 to 5 years of age should sleep 10 to 13 hours per 24 hours (including naps) on a regular basis to promote optimal health. Children 6 to 12 years of age should sleep 9 to 12 hours per 24 hours on a regular basis to promote optimal health. Teenagers 13 to 18 years of age should sleep 8 to 10 hours per 24 hours on a regular basis to promote optimal health. Sleeping the number of recommended hours on a regular basis is associated with better health outcomes including: improved attention, behavior, learning, memory, emotional regulation, quality of life, and mental and physical health. Regularly sleeping fewer than the number of recommended hours is associated with attention, behavior, and learning problems. Insufficient sleep also increases the risk of accidents, injuries, hypertension, obesity, diabetes, and depression. Insufficient sleep in teenagers is associated with increased risk of self-harm, suicidal thoughts, and suicide attempts. COMMENTARY: A commentary on this article apears in this issue on page 1439.

TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features.

OBJECTIVE: To evaluate the phenotypic spectrum associated with mutations in TBC1D24. METHODS: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24). RESULTS: Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function. CONCLUSIONS: TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes.

Pediatric Sleep Pharmacology: A Primer.

"What will you give my child to help him sleep?" is a common question parents ask and some health care providers abhor hearing. Entire families may suffer when one member does not sleep well. Poor sleep may complicate the management of other comorbid conditions. Health care providers may have received only limited education on sleep disorders and are frequently forced to choose between treatment options that are poorly studied in children. Fortunately, when addressed correctly, many children with chronic sleep disorders may improve their sleep and daytime behavior in a relatively short time. This review provides a framework to help understand the causes of poor sleep in children and the potential pharmacologic options.

Quality measures for the care of pediatric patients with obstructive sleep apnea.

ABSTRACT: The Board of Directors of the American Academy of Sleep Medicine (AASM) commissioned a Task Force to develop quality measures as part of its strategic plan to promote high quality patient-centered care. Among many potential dimensions of quality, the AASM requested Workgroups to develop outcome and process measures to aid in evaluating the quality of care of five common sleep disorders: insomnia, obstructive sleep apnea in adults, obstructive sleep apnea in children, restless legs syndrome, and narcolepsy. This paper describes the rationale, background, general methods development, and considerations in implementation of these quality measures in obstructive sleep apnea (OSA) in children. This document describes measurement methods for five desirable process measures: assessment of symptoms and risk factors of OSA, initiation of an evidence-based action plan, objective evaluation of high-risk children with OSA by obtaining a polysomnogram (PSG), reassessment of signs and symptoms of OSA within 12 months, and documentation of objective assessment of positive airway pressure adherence. When these five process measures are met, clinicians should be able to achieve the two defined outcomes: improve detection of childhood OSA and reduce signs and symptoms of OSA after initiation of a management plan. The AASM recommends the use of these measures as part of quality improvement programs that will enhance the ability to improve care for patients with childhood OSA.

Lennox-Gastaut syndrome symptomatic to hypothalamic hamartoma: evolution and long-term outcome following surgery.

BACKGROUND: Lennox-Gastaut syndrome is a catastrophic childhood cryptogenic or symptomatic epilepsy. Hypothalamic hamartomas cause refractory epilepsy often consistent with Lennox-Gastaut syndrome. METHODS: Children with Lennox-Gastaut syndrome were defined by a triad of multiple generalized seizure types, slow spike-and-wave on EEG, and mental retardation. RESULTS: Twenty-one of 159 hypothalamic hamartoma patients (14%) met the diagnostic criteria of Lennox-Gastaut syndrome. The median age of patients at epilepsy onset was 0.9 years (range, birth to 9 years). Six of the 21 patients (28%) had preceding infantile spasms. All patients underwent different surgical approaches, including endoscopic, transcallosal, orbitozygomatic resections, and radiosurgery treatment. Five of the 21 (24%) were seizure free with an additional 9 (42%) having at least >90% seizure reduction. Only 1 patient was not effectively treated (<50% seizure reduction). Eighty-eight percent of parents reported improvement in behavioral functioning. Shorter duration of epilepsy prior to surgery was a significant predictor of surgical outcome. CONCLUSIONS: Patients with Lennox-Gastaut syndrome symptomatic to hypothalamic hamartomas have better postsurgical outcome due to other etiologies compared with cryptogenic and symptomatic Lennox-Gastaut syndrome patients. However, compared with overall hypothalamic hamartomas postsurgical outcomes, this cohort was less favorable. Earlier surgery may lead to better outcomes.