The effects of daylight duration on the multiple sleep latency test (MSLT) results: A pilot study.

OBJECTIVE: MSLT results are known to be affected by multiple factors including sleep time, frequency of nighttime arousals, and medications intake. Although being the main synchronizer of sleep and wakefulness, daylight duration effects on MSLT have not been examined. Burlington, Vermont, USA experiences great variations in daylight duration, ranging from 8 h 50 min to 15 h 33 min of daylight. The aim of this study was to test the hypothesis that there would be photoperiod duration effects on MSLTs performed during short daylight (short daylight studies, SDS) vs. long daylight (long daylight studies, LDS) from 2013 to 2023 in our sleep laboratory. METHODS: We identified and analyzed 37 SDS (daylight 530-560 min) and 36 LDS (daylight 903-933 min) from our database. Groups of SDS and LDS results were compared using non-paired student T test, Chi-Square and non-parametric Mann Whitney U Test. RESULTS: Average daylight duration was 15 h 18 ± 14.6 min for LDS and 8 h 57 ± 18 min for SDS. Two groups did not differ in terms of the age, gender, BMI and race of patients studied. Mean total sleep time and sleep efficiency during PSG preceding MSLT, and MSLT mean sleep onset latency did not significantly differ for the two groups. However, SDS MSLT naps had significantly more sleep onset REM periods (SOREMP), and distribution of the number of SOREMP captured during MSLT was different for SDS and LDS groups. Differences of SDS and LDS results did not relate to sleep architecture of the overnight PSG as analysis of sleep and REM latency and relative percentages of N1, N2, REM, and N3 was not significantly different between SDS and LDS. The two groups showed difference in arousal indexes during N1 and REM sleep. CONCLUSIONS: Daylight duration may impact MSLT results and should probably be accounted for in MSLT interpretation. Attention to photoperiod could be considered in MSLT guidelines, if our results are replicated in larger samples.

Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine.

This article updates the American Academy of Sleep Medicine protocols for the administration of the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. The American Academy of Sleep Medicine commissioned a task force of clinical experts in sleep medicine to review published literature on the performance of these tests since the publication of the 2005 American Academy of Sleep Medicine practice parameter paper. Although no evidence-based changes to the protocols were warranted, the task force made several changes based on consensus. These changes included guidance on patient preparation, medication and substance use, sleep before testing, test scheduling, optimum test conditions, and documentation. This article provides guidance to providers who order and administer the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. CITATION: Krahn LE, Arand DL, Avidan AY, et al. Recommended protocols for the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine. J Clin Sleep Med. 2021;17(12):2489-2498.

The Assessment and Treatment of Sleep Abnormalities in Children and Adolescents with Autism Spectrum Disorder: A Review.

OBJECTIVE: To summarize causes, evaluation methods, and treatment of sleep disturbance in children and adolescents with autism spectrum disorder (ASD). METHODS: A narrative literature and synthesis approach was used. RESULTS/DISCUSSION: Sleep disturbances in this population are common and include insomnia, parasomnias, circadian rhythm disorders, and sleep-related movement disorders. Multiple factors may contribute to the higher rates of sleep disturbances in persons with ASD. Unfortunately, there are not evidence-based guidelines specific for the management of these sleep disorders in this population. There is also a lack of controlled clinical studies. Nevertheless, assessment of sleep problems using both subjective and objective methods are recommended to develop an individualized approach. Behavioural interventions are preferred first line treatment for insomnia. As adjunctive measures, pharmacotherapy may be warranted and choice should be guided based on accompanying symptoms. The most commonly used pharmacotherapy for sleep disturbance, primarily insomnia, include melatonin and alpha agonists. Not all currently used medications are approved for use for children and adolescents.

OBJECTIF: Résumer les causes, les méthodes d'évaluation et de traitement des troubles du sommeil chez les enfants et les adolescents souffrant du trouble du spectre de l'autisme (TSA). MÉTHODES: une littérature narrative et une approche de synthèse ont été utilisées. RÉSULTATS/DISCUSSION: les troubles du sommeil dans cette population sont communs et comprennent l'insomnie, la parasomnie, les perturbations du rythme circadien, et le trouble du mouvement lié au sommeil. De multiples facteurs peuvent contribuer aux taux élevés de troubles du sommeil chez les personnes souffrant du TSA. Malheureusement il n'existe pas de directives fondées sur des données probantes pour la prise en charge de ces troubles du sommeil dans cette population. Il manque également des études cliniques contrôlées. Néanmoins, l'évaluation des troubles de sommeil à l'aide de méthodes tant subjectives qu'objectives est recommandée pour développer une approche individualisée. Les interventions comportementales sont le traitement de première intention préféré pour l'insomnie. La pharmacothérapie des mesures d'appoint peut être justifiée et le choix devrait être basé sur les symptômes accompagnateurs. La pharmacothérapie la plus utilisée pour les troubles du sommeil, surtout l'insomnie, comprend la mélatonine et les alpha-agonistes. Les médicaments couramment en usage ne sont pas tous approuvés à utiliser pour les enfants et les adolescents.

Alternative Approaches to Adenotonsillectomy and Continuous Positive Airway Pressure (CPAP) for the Management of Pediatric Obstructive Sleep Apnea (OSA): A Review.

Continuous positive airway pressure (CPAP) is considered first-line treatment in the management of pediatric patients without a surgically correctible cause of obstruction who have confirmed moderate-to-severe obstructive sleep apnea (OSA). The evidence supports its reduction on patient morbidity and positive influence on neurobehavioral outcome. Unfortunately, in clinical practice, many patients either refuse CPAP or cannot tolerate it. An update on alternative approaches to CPAP for the management of OSA is discussed in this review, supported by the findings of systematic reviews and recent clinical studies. Alternative approaches to CPAP and adenotonsillectomy for the management of OSA include weight management, positional therapy, pharmacotherapy, high-flow nasal cannula, and the use of orthodontic procedures, such as rapid maxillary expansion and mandibular advancement devices. Surgical procedures for the management of OSA include tongue-base reduction surgery, uvulopalatopharyngoplasty, lingual tonsillectomy, supraglottoplasty, tracheostomy, and hypoglossal nerve stimulation. It is expected that this review will provide an update on the evidence available regarding alternative treatment approaches to CPAP for clinicians who manage patients with pediatric OSA in daily clinical practice.

Cumulative Incidence of Seizures and Epilepsy in Ten-Year-Old Children Born Before 28 Weeks' Gestation.

OBJECTIVE: We evaluated the incidence of seizures and epilepsy in the first decade of life among children born extremely premature (less than 28 weeks' gestation). METHOD: In a prospective, multicenter, observational study, 889 of 966 eligible children born in 2002 to 2004 were evaluated at two and ten years for neurological morbidity. Complementing questionnaire data to determine a history of seizures, all caregivers were interviewed retrospectively for postneonatal seizures using a validated seizure screen followed by a structured clinical interview by a pediatric epileptologist. A second pediatric epileptologist established an independent diagnosis based on recorded responses of the interview. A third epileptologist determined the final diagnosis when evaluators disagreed (3%). Life table survival methods were used to estimate seizure incidence through ten years. RESULTS: By age ten years, 12.2% (95% confidence interval: 9.8, 14.5) of children had experienced one or more seizures, 7.6% (95% confidence interval: 5.7, 9.5) had epilepsy, 3.2% had seizure with fever, and 1.3% had a single, unprovoked seizure. The seizure incidence increased with decreasing gestational age. In more than 75% of children with seizures, onset was after one year of age. Seizure incidence was comparable in both sexes. Two-thirds of those with epilepsy had other neurological disorders. One third of children with epilepsy were not recorded on the medical history questionnaire. SIGNIFICANCE: The incidence of epilepsy through age ten years among children born extremely premature is approximately 7- to 14-fold higher than the 0.5% to 1% lifetime incidence reported in the general pediatric population. Seizures in this population are under-recognized, and possibly underdiagnosed, by parents and providers.

"More than Meets the Eye": When the Neonatal Course May Impact Several Years Out.

CASE: Nadia is a 7-year-old girl who you have followed since her discharge from the Neonatal Intensive Care Unit (NICU). Her parents are here today for an urgent visit with behavioral concerns, such as inattention, hyperactivity, and aggression.Nadia is a former 40-weeker born through vacuum-assisted vaginal delivery at 9 pounds 7 ounces. Her delivery was complicated with shoulder dystocia, which resulted in resuscitation. Her Apgar scores were 1, 3, and 4 at 1, 5, and 10 minutes, respectively. After intubation and stabilization on mechanical ventilation, Nadia was transferred to the NICU. Her neonatal course included systemic hypothermia using "cool cap" for hypoxic-ischemic encephalopathy (HIE) for a duration of 72 hours. She was extubated on day of life 3. She had an occupational therapy consultation for poor suck/feeding, and it quickly improved. She was discharged on day of life 14. On discharge, Nadia was referred to early intervention (EI) and the NICU follow-up clinic. Nadia was followed by EI until 12 months of age and in the NICU follow-up clinic until 18 months of age, as there were no concerns meeting her developmental milestones or her neuromotor development.At this urgent visit, Nadia's parents report that she attended a family child care from 1.5 to 3 years of age, Head Start from 3 to 5 years of age and the local public school from 5 years to present. Since starting child care, Nadia's teachers have reported that she requires a lot of redirection and refocusing, fidgets a lot in class, and can be aggressive toward her peers when unprovoked. Since her parents had not seen these behaviors at home, they thought it was a phase that she would grow out of. However, as they began to work with her to complete school assignments, they noticed that it was very difficult for Nadia to sit still and focus on work. They also struggled in the mornings to get her ready and off to school.The parents bring in Conners scales completed by themselves and her lead teacher, and with these and our clinical observations, we diagnose her with attention-deficit/hyperactivity disorder (ADHD), combined type. We discuss risk factors and ADHD management with her parents. During our discussion, Nadia's father, who has done some reading on ADHD, remembers reading an article about HIE and NICU stay being risk factors for ADHD. He wonders if this affects the choice of management of her ADHD symptoms. How would you address his query?

A Novel Parent Questionnaire for the Detection of Seizures in Children.

BACKGROUND: We developed a seizure questionnaire that could be administered by a trained research assistant in a two-step process, approximating the clinical diagnostic process of a pediatric epileptologist. This questionnaire was designed to study seizure prevalence in a research population of 10-year-old children at risk for epilepsy. METHODS: English-speaking parents of children 6 months to 12 years old were recruited from the pediatric neurology clinics at Boston Medical Center and interviewed using a computerized questionnaire. An algorithm of parent responses rendered a 4-level ranking scale of seizure probability for events: (1) not likely, (2) indeterminate, (3) probable, (4) almost certain. Blinded to questionnaire results, pediatric neurologists served as the diagnostic gold standard, ranking each patient event using the same four-level scale based on clinical history and examination. RESULTS: The questionnaire was completed by 150 of 177 (84.7%) enrolled parents. Seizure prevalence among participants was 38.6%. The seizure questionnaire yielded a fitted receiver operating characteristic area of 0.93 (95% confidence interval [CI], 0.89-0.97). Based on optimal sensitivity and false-positive fraction, we dichotomized the questionnaire results as consistent with seizure (levels 3 and 4) or without seizure (levels 1 and 2). Overall, findings included a 91.4% sensitivity (95% CI, 84.2%-98.6%) and an 82.6% specificity (95% CI, 74.9%-90.4%). The positive predictive value was 76.8% (95% CI, 66.9%-86.8%) and the negative predictive value was 93.8% (95% CI, 88.6%-99.1%). CONCLUSIONS: This pediatric seizure questionnaire was both sensitive and specific for detecting clinically confirmed seizures. This tool may be useful to researchers and clinicians in screening large populations of children, decreasing the time and cost of added neurological assessments.

"More than meets the eye": when the neonatal course may impact several years out.

CASE: Nadia is a 7-year-old girl who you have followed since her discharge from the Neonatal Intensive Care Unit (NICU). Her parents are here today for an urgent visit with behavioral concerns, such as inattention, hyperactivity, and aggression.Nadia is a former 40-weeker born through vacuum-assisted vaginal delivery at 9 pounds 7 ounces. Her delivery was complicated with shoulder dystocia, which resulted in resuscitation. Her Apgar scores were 1, 3, and 4 at 1, 5, and 10 minutes, respectively. After intubation and stabilization on mechanical ventilation, Nadia was transferred to the NICU. Her neonatal course included systemic hypothermia using "cool cap" for hypoxic-ischemic encephalopathy (HIE) for a duration of 72 hours. She was extubated on day of life 3. She had an occupational therapy consultation for poor suck/feeding, and it quickly improved. She was discharged on day of life 14. On discharge, Nadia was referred to early intervention (EI) and the NICU follow-up clinic. Nadia was followed by EI until 12 months of age and in the NICU follow-up clinic until 18 months of age, as there were no concerns meeting her developmental milestones or her neuromotor development.At this urgent visit, Nadia's parents report that she attended a family child care from 1.5 to 3 years of age, Head Start from 3 to 5 years of age and the local public school from 5 years to present. Since starting child care, Nadia's teachers have reported that she requires a lot of redirection and refocusing, fidgets a lot in class, and can be aggressive toward her peers when unprovoked. Since her parents had not seen these behaviors at home, they thought it was a phase that she would grow out of. However, as they began to work with her to complete school assignments, they noticed that it was very difficult for Nadia to sit still and focus on work. They also struggled in the mornings to get her ready and off to school.The parents bring in Conners scales completed by themselves and her lead teacher, and with these and our clinical observations, we diagnose her with attention-deficit/hyperactivity disorder (ADHD), combined type. We discuss risk factors and ADHD management with her parents. During our discussion, Nadia's father, who has done some reading on ADHD, remembers reading an article about HIE and NICU stay being risk factors for ADHD. He wonders if this affects the choice of management of her ADHD symptoms. How would you address his query?

Prenatal protein malnutrition alters the proportion but not numbers of parvalbumin-immunoreactive interneurons in the hippocampus of the adult Sprague-Dawley rat.

Prenatal protein malnutrition alters the structure and function of the adult rat hippocampal formation. The current study examines the effect of prenatal protein malnutrition on numbers of parvalbumin-immunoreactive (PV-IR) GABAergic interneurons, which are important for perisomatic inhibition of hippocampal pyramidal neurons. Brain sections from prenatally protein malnourished and normally nourished rats were stained for parvalbumin and PV-IR neurons were quantified using stereology in the dentate gyrus, CA3/2 and CA1 subfields, and the subiculum for both cerebral hemispheres. Results demonstrated that prenatal malnutrition did not affect the number of PV-IR interneurons in the hippocampus. Since prenatal protein malnutrition reduces total neuron numbers in the CA1 subfield (1), this results in an altered ratio of PV-IR interneurons to total neuronal numbers (from 1:22.9 in controls to 1:20.5 in malnourished rats). Additionally, there was no hemispheric asymmetry of either PV-IR neuron numbers or ratio of PV-IR:total neuron numbers.

Asymmetry of neuron numbers in the hippocampal formation of prenatally malnourished and normally nourished rats: a stereological investigation.

There is considerable evidence for lateralization of hippocampal function and hemispheric asymmetry in humans. In the rat, studies have reported asymmetries in the thicknesses of layers, the volumes of hippocampal subfields, and the density of cells at specific points along the septotemporal axis. To determine if there is an asymmetry of neuron numbers and whether prenatal malnutrition affects any asymmetries, 90-day old male Sprague-Dawley rats that were either normally nourished or malnourished prenatally were perfused with 4% paraformaldehyde and the brains cut into 30-micro m sections. One interrupted series of sections through the entire hippocampus was analyzed stereologically to estimate the total number of neurons in the hilus of the dentate gyrus, the CA3/CA2 stratum pyramidale (SP), the CA1 SP, and the SP of the prosubiculum/subiculum of both hemispheres. Significant asymmetries (P < 0.05) were found in the CA1 and CA3/CA2 subfields, with the right hemisphere containing 21 and 6% fewer neurons, respectively. Malnutrition reduced neuron numbers in the CA1 subfield by 12%, but did not alter the hemispheric asymmetry. Our findings agree with previous reports of left dominant asymmetries in the rat brain and suggest that this may result from differences in total numbers of neurons.

Effect of prenatal protein malnutrition on numbers of neurons in the principal cell layers of the adult rat hippocampal formation.

Malnutrition has been associated with a variety of functional and anatomical impairments of the hippocampal formation. One of the more striking of these is widespread loss of hippocampal neurons in postnatally malnourished rats. In the present study we have investigated the effect of prenatal malnutrition on these same neuronal populations, neurons that are all generated during the period of the dietary restriction. In prenatally protein deprived rats, using design-based stereology, we have measured the regional volume and number of neurons in the hilus of the dentate gyrus and the pyramidal cell layers of CA3, CA2, CA1, and the subiculum of 90-day-old animals. These results demonstrated a statistically significant reduction of 20% in neuron numbers in the CA1 subfield, while numbers in the other subfields were unchanged. There was a corresponding significant reduction of 22% in the volume of the CA1 subfield and a significant 14% decrease in the volume of the pyramidal layer of the subiculum. The change in volume of the pyramidal layer of the subiculum without neuron loss may reflect loss of CA1 afferent input to the pyramidal layer. Although the effect of nutritional deprivation on the neuronal population appears to be different in pre- and postnatal malnutrition, both dietary paradigms highlight the vulnerability of key components of the hippocampal trisynaptic circuit (consisting of the dentate granule cell mossy fibers projection to CA3 pyramids and the CA3 projection to the CA1 pyramids), which is an essential circuit for memory and learning.

Effects of prenatal protein malnutrition and acute postnatal stress on granule cell genesis in the fascia dentata of neonatal and juvenile rats.

Although postnatal genesis of granule cells in the hippocampal fascia dentata is known to be influenced by prenatal protein deprivation or by stress, the combined effects of prenatal protein malnutrition and stress on these cells are unknown. This study was designed to examine this combined effect. Well-nourished and prenatally malnourished pups on postnatal day 7 (P7) were stressed by maternal separation and reduction of body temperature and on postnatal day 30 (P30) by immobilization with restraint. Bromodeoxyuridine (BrDU) was injected at the time of stress, and 2 h later, the numbers of immunolabeled cells were quantified by standard stereological techniques. In comparison to controls, prenatally malnourished rats showed a significantly lower number of cells tagged in the fascia dentata on P7 (p < or =0.05), and a significantly higher number of cells (p < or =0.05) on P30. In both age groups, control rats exposed to acute stress showed a significantly decreased number of cells tagged in the fascia dentata (p < or =0.05). In contrast, neurogenesis in malnourished rats was not significantly affected by acute stress at either age. Thus, the pattern of neurogenesis in the fascia dentata and its response to stress has been fundamentally altered by prenatal protein deprivation.