Elena Finotti

Clinical and polysomnographic course of childhood narcolepsy with cataplexy

Our aim was to investigate the natural evolution of cataplexy and polysomnographic features in untreated children with narcolepsy with cataplexy. To this end, clinical, polysomnographic, and cataplexy-video assessments were performed at diagnosis (mean age of 10 ± 3 and disease duration of 1 ± 1 years) and after a median follow-up of 3 years from symptom onset (mean age of 12 ± 4 years) in 21 children with narcolepsy with cataplexy and hypocretin 1 deficiency (tested in 19 subjects). Video assessment was also performed in two control groups matched for age and sex at first evaluation and follow-up and was blindly scored for presence of hypotonic (negative) and active movements. Patients’ data at diagnosis and at follow-up were contrasted, compared with controls, and related with age and disease duration. At diagnosis children with narcolepsy with cataplexy showed an increase of sleep time during the 24 h; at follow-up sleep time and nocturnal sleep latency shortened, in the absence of other polysomnographic or clinical (including body mass index) changes. Hypotonic phenomena and selected facial movements decreased over time and, tested against disease duration and age, appeared as age-dependent. At onset, childhood narcolepsy with cataplexy is characterized by an abrupt increase of total sleep over the 24 h, generalized hypotonia and motor overactivity. With time, the picture of cataplexy evolves into classic presentation (i.e. brief muscle weakness episodes triggered by emotions), whereas total sleep time across the 24 h decreases, returning to more age-appropriate levels.

High Prevalence of Precocious Puberty and Obesity in Childhood Narcolepsy with Cataplexy

STUDY OBJECTIVES We analyzed the potential predictive factors for precocious puberty, observed in some cases of childhood narcolepsy with cataplexy (NC) and for obesity, a much more common feature of NC, through a systematic assessment of pubertal staging, body mass index (BMI), and metabolic/endocrine biochemical analyses. DESIGN Cross-sectional on consecutive recruitment. SETTING Hospital sleep center and pediatric unit. PATIENTS Forty-three children and adolescents with NC versus 52 age-matched obese children as controls. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Patients underwent clinical interview, polysomnographic recordings, cerebrospinal fluid hypocretin-1 measurement, and human leukocyte antigen typing. Height, weight, arterial blood pressure, and Tanner pubertal stage were evaluated. Plasma lipid and glucose profiles were analyzed. When an altered pubertal development was clinically suspected, plasma concentrations of hypothalamic-pituitary-gonadal axis hormones were determined. Children with NC showed a high prevalence of overweight/obesity (74%) and a higher occurrence of precocious puberty (17%) than obese controls (1.9%). Isolated signs of accelerated pubertal development (thelarche, pubic hair, advanced bone age) were also present (41%). Precocious puberty was significantly predicted by a younger age at first NC symptom onset but not by overweight/obesity or other factors. In addition, overweight/obesity was predicted by younger age at diagnosis; additional predictors were found for overweight/obesity (short disease duration, younger age at weight gain and lower high-density lipoprotein cholesterol), which did not include precocious puberty. NC symptoms, pubertal signs appearance, and body weight gain developed in close temporal sequence. CONCLUSIONS NC occurring during prepubertal age is frequently accompanied by precocious puberty and overweight/obesity, suggesting an extended hypothalamic dysfunction. The severity of these comorbidities and the potential related risks require a multidiagnostic approach and a tailored therapeutic management.

NREM sleep instability in children with sleep terrors: The role of slow wave activity interruptions

OBJECTIVE To evaluate NREM sleep instability, as measured by the cyclic alternating pattern (CAP), in children with sleep terrors (ST) vs. normal controls. METHODS Ten boys (mean age: 8.5 years, range 5-13) meeting the following inclusion criteria: (a) complaint of ST several times a month, (b) a history of ST confirmed by a third person, and (c) a diagnosis of ST according to the ICSD-2 criteria. Eleven age-matched control children with parental report of at least 8.5h of nightly sleep, absence of known daytime consequences of sleep disorders were recruited by advertisement from the community. Sleep was visually scored for sleep macrostructure and CAP using standard criteria. RESULTS Sleep macrostructure showed only a significantly increased number of awakenings per hour and reduced sleep efficiency in ST subjects. CAP parameters analysis revealed several significant differences in ST vs. controls: an increase of total CAP rate in SWS, of A1 index in SWS and of the mean duration of A phases while B phases had a decreased duration, exclusively in SWS. The normalized CAP interval-distribution graphs showed significant differences in SWS with interval classes 10< or = i < 35s higher in children with ST and intervals classes above 50s higher in normal controls. CONCLUSIONS Children with ST showed faster alternations of the amplitude of slow EEG bursts during SWS. This abnormally fast alternation of the EEG amplitude in SWS is linked to the frequent intrusion of CAP B phases interrupting the continuity of slow delta activity and could be considered as a neurophysiological marker of ST. SIGNIFICANCE This abnormal alternation of the EEG amplitude in SWS is associated with the occurrence of parasomnias and might be considered as a neurophysiological marker of disorders of arousal.

Tolerance and efficacy of sodium oxybate in childhood narcolepsy with cataplexy: a retrospective study.

Narcolepsy with cataplexy is a sleep disorder characterized by excessive daytime sleepiness, irresistible sleep episodes, and sudden loss of muscle tone (cataplexy) mostly triggered by emotions. Narcolepsy with cataplexy is a disabling lifelong disorder frequently arising during childhood. Pediatric narcolepsy often results in severe learning and social impairment. Improving awareness about this condition increases early diagnosis and may allow patients to rapidly access adequate treatments, including pharmacotherapy and/or non-medication-based approaches. Even though children currently undergo pharmacotherapy, data about safety and efficacy in the pediatric population are scarce. Lacking international guidelines as well as drugs registered for childhood narcolepsy with cataplexy, physicians have no other alternative but to prescribe in an off-label manner medications identical to those recommended for adults. We retrospectively evaluated 27 children ranging from 6 to 16 years old, suffering from narcolepsy with cataplexy, who had been treated with off-label sodium oxybate and had been followed in a clinical setting. Throughout a semi-structured interview, we documented the good efficacy and tolerability of sodium oxybate in the majority of the patients. This study constitutes a preliminary step towards a further randomized controlled trial in childhood narcolepsy with cataplexy.

Long‐term outcome and risk of oesophageal cancer after surgery for achalasia

Few studies have reported very long‐term results after surgery for oesophageal achalasia. The aim of the present study was to assess long‐term subjective outcomes after cardiomyotomy and partial fundoplication, focusing specifically on the risk of oesophageal cancer.

Slow EEG Amplitude Oscillations During NREM Sleep and Reading Disabilities in Children With Dyslexia

Study Objectives: To analyze non-rapid eye movement (NREM) sleep microstructure of children with dyslexia, by means of cyclic alternating pattern (CAP) analysis and to correlate CAP parameters with neuropsychological measures. Design: Cross-sectional study using polysomnographic recordings and neuropsychological assessments. Setting: Sleep laboratory in academic center. Participants: Sixteen subjects with developmental dyslexia (mean age 10.8 years) and 11 normally reading children (mean age 10.1 years) underwent overnight polysomnographic recording. Intervention: N/A. Measurements and Results: Sleep architecture parameters only showed some statistically significant differences: number of sleep stage shifts per hour of sleep, percentage of N3, and number of R periods were significantly lower in dyslexic children versus controls. CAP analysis revealed a higher total CAP rate and A1 index in stage N3. A2% and A2 index in stage N2 and N3 were lower in dyslexic children while no differences were found for A3 CAP subtypes. The correlation analysis between CAP parameters and cognitive-behavioral measures showed a significant positive correlation between A1 index in N3 with Verbal IQ, full-scale IQ, and Memory and Learning Transfer reading test; while CAP rate in N3 was positively correlated with verbal IQ. Conclusions: To overcome reading difficulties, dyslexic subjects overactivate thalamocortical and hippocampal circuitry to transfer information between cortical posterior and anterior areas. The overactivation of the ancillary frontal areas could account for the CAP rate modifications and mainly for the increase of CAP rate and of A1 index in N3 that seem to be correlated with IQ and reading abilities.

Psychosocial Profile and Quality of Life in Children With Type 1 Narcolepsy: A Case-Control Study

STUDY OBJECTIVES To investigate behavioral aspects and quality of life in children and adolescents with type 1 narcolepsy (NT1). METHODS We performed a case-control study comparing 29 patients with NT1 versus sex- and age-matched patients with idiopathic epilepsy (n = 39) and healthy controls (n = 39). Behavior and quality of life were evaluated by self-administered questionnaires (Child Behavior Checklist, Pediatric Quality of Life Inventory). Patient groups were contrasted and scale results were correlated with clinical and polysomnographic parameters, and cerebrospinal fluid hypocretin-1 levels. RESULTS Young patients with NT1 showed increased internalizing problems associated with aggressive behavior. Emotional profile in patients with NT1 positively correlated with age at onset, diagnostic delay, and subjective sleepiness, whereas treatment and disease duration were associated with fewer behavioral problems (attention problems, aggressive behavior, and attention deficit/hyperactivity disorder). Psychosocial health domains of pediatric NT1 were worse than in healthy controls, whereas the physical health domains were comparable. CONCLUSIONS Young NT1 patients show a discrete pattern of altered behavioral, thought, and mood profile in comparison with healthy controls and with idiopathic epilepsy patients thus suggesting a direct link with sleepiness. Further studies investigating behavior in patients with idiopathic hypersomnia or type 2 narcolepsy are needed to disentangle the role of REM sleep dysfunction and hypocretin deficiency in psychiatric disorders. Symptoms of withdrawal, depression, somatic complaints, thought problems, and aggressiveness were common, NT1 children perceived lower school competencies than healthy children, and their parents also reported worse psychosocial health. Our data suggest that early effective treatment and disease self-awareness should be promoted in NT1 children for their positive effect on behavior and psychosocial health.

All-night EEG power spectral analysis of the cyclic alternating pattern at different ages

OBJECTIVE To analyze in detail the frequency content of the different EEG components of the Cyclic Alternating Pattern (CAP) in the whole sleep of pre-school and school age children compared to normal young adults. METHODS Fourteen pre-school age and 18 school age children and 16 adults were included in this study. Each participant underwent a polysomnographic overnight recording, after an adaptation night; sleep stages and CAP were scored following standard criteria. Average spectra were obtained for each CAP condition from the signal recorded from C3/A2 or C4/A1, separately in sleep stage 2 and slow-wave sleep (SWS), for each subject. RESULTS The analysis of the relative power density in the three groups showed that in sleep stage 2 and in SWS, CAP A1, A2, A3 subtypes had a significantly higher power in all frequency ranges in pre-school children than in adults, while school children differed mainly for the lower frequencies (<7 Hz). For non-CAP, pre-school and school children differed from adults at almost all frequencies analyzed. Generally, A1, A2 and A3 showed clear spectral differences in the three different groups of subjects with pre-school age children showing slightly less evident differences. CONCLUSIONS CAP subtypes are characterized by clearly different spectra at different ages and also the same subtype shows a different power spectrum, during sleep stage 2 or SWS. This study shows that pre-school children have a different structure of sleep, especially from the microstructural (CAP) point of view: the differences are evident for all the CAP components and for non-CAP in almost all the frequency bands. This finding might be associated to the age-related delta decline in the 0-3 Hz frequency reported in children of the same age. SIGNIFICANCE Our data seem to provide information not available before and useful for the understanding of the impact of CAP on the sleep EEG neurophysiological dynamics at different ages. This type of information is crucial for a more adequate interpretation of data provided by a growing number of studies analyzing CAP in groups of pediatric patients.

Mapping changes in cortical activity during sleep in the first 4 years of life

A coherent body of evidence supports the notion that sleep is a local and use‐dependent process. Significant changes in brain morphology and function occur in the first years of life, revealing a postero–anterior trajectory of cortical maturation. On this basis, a recent study demonstrated that regional cortical maturation between early childhood and late adolescence is reflected in regional changes of sleep slow wave activity (SWA) during non‐rapid eye movement (NREM) sleep. Our hypothesis is that changes of electroencephalogram (EEG) rhythms during sleep from birth to childhood are also mirrored by parallel regional changes in the EEG rhythms of sleep according to the assumption of a postero–anterior gradient in cortical maturation. We studied all‐night EEG of 39 healthy, full‐term, infants and children aged between 0 and 48 months, evaluating regional differences in NREM sleep. We confirmed the strictly local nature of sleep with frequency‐specific regional differences. Specifically, we found a general shift of maxima of the upper alpha activity from occipital to prefrontal regions, expressed mainly by the ~11 Hz frequency. This shift corresponds to a postero–anterior trajectory of the so‐called ‘slow spindles’. The theta and alpha EEG activity of the frontal cortex exhibits a clear, positive, correlation with age. We conclude that specific local differences during NREM sleep, parallel cortical maturation also in the first 4 years of life.

455 Laparoscopic Heller Myotomy Can Be Used As Primary Therapy for Esophageal Achalasia Regardless of Age

Introduction Laparoscopic Heller-Dor surgery is the current treatment of choice for patients with esophageal achalasia, but elderly patients are generally referred for less invasive treatments (pneumatic dilations or botulinum toxin injections).