TSC1 as a Novel Gene for Sleep-Related Hypermotor Epilepsy: A Child with a Mild Phenotype of Tuberous Sclerosis.

Sleep-related hypermotor epilepsy (SHE) is a rare syndrome that presents with hyperkinetic asymmetric tonic/dystonic seizures with vegetative signs, vocalization, and emotional facial expression, mainly during light non-rapid eye movement sleep stages. The role of various genes (CHRNA4, CHRNB2, CHRNA2, KCNT1, DEPDC5, NPRL2, NPRL3, and PRIMA1) has previously been reported, though genetic etiology is assessed in less than 10% of cases. We report the case of a 5-year-old female carrying the TSC1 variant c.843del p.(Ser282Glnfs*36) who presented with a mild phenotype of tuberous sclerosis, including carbamazepine-responsive SHE, normal neurocognitive functioning, hypomelanotic macules, no abnormalities outside the central nervous system, and tubers at neuroimaging. The presented case extends the list of SHE-related genes to include TSC1, thus suggesting a central pathogenic role of mammalian target of rapamycin (mTOR) cascade dysfunction in SHE and introducing a possible use of mTOR inhibitors in this epileptic syndrome.

Kambakutaisoto Treatment for Children With Night Crying and Arousal Parasomnias Developed During Prolonged Hospitalization for Hematological and Oncological Diseases.

OBJECTIVE: The lack of an established treatment standard prompted an examination of whether kambakutaisoto, an herbal formula, is effective for non-rapid eye movement (NREM)-related parasomnias and night crying (provisionally defined as an infantile form of arousal parasomnia). METHODS: This study included 137 children aged median 4.1 years (range, 0.02-18.5) who were admitted for hematological and oncological diseases. RESULTS: Of 137, 3 children developed recurrent episodes of NREM-related parasomnias, and 3 developed night crying. The proportion of children with night-crying/parasomnia receiving invasive procedures was significantly higher than those without (100% vs. 47%, P = .013). All 6 children with night crying/parasomnia received kambakutaisoto at a dose of 0.13-0.22 g/kg per os and responded from the start of administration with a significant reduction in the number of episodes. No adverse effects were observed. CONCLUSION: Kambakutaisoto may be a safe and promising therapy for night crying and NREM-related parasomnias in children.

Intake of stimulant foods is associated with development of parasomnias in children / Ingestão de alimentos estimulantes está associada ao desenvolvimento de parassonias em crianças

ABSTRACT Objective To verify if nighttime feeding habits can influence parasomnia in children. Method Seven private and four public Elementary Schools took part in the study. A total of 595 Sleep Disturbance Scale for Children were distributed to the parents of children aged from 7 to 8 years. Data of dietary recall, starting time to school, physical activity, and nutritional status were studied. Results Of the 226 questionnaires completed, 92 (41%) reported parasomnia. Girls had 2.3 times more the chance to parasomnia than boys. Children who consumed stimulant foods had 2.6 times more chance to have parasomnia than those of children who consumed non-stimulant foods. There were no difference between parasomnia and no-parasomnia groups in food type (p = 0.78) or timing of last meal before bedtime (p = 0.50). Conclusion Our findings suggest that intake of stimulant foods is associated with development of parasomnia in children.

RESUMO Objetivo Verificar se hábitos de alimentação noturna influenciam parassonias em crianças. Método Sete escolas privadas e quatro públicas, de Ensino Fundamental, fizeram parte do estudo. Um total de 595 Escalas de Distúrbio do Sono para Crianças foram distribuídas para os pais de crianças entre 7 e 8 anos. Dados de recordatório alimentar, período escolar, atividade física e estado nutricional foram estudados. Resultados Dos 226 questionários preenchidos, 92 (41%) relataram presença de parassonias. Meninas tiveram 2,3 vezes mais chance de parassonias e crianças que consumiram alimentos estimulantes tiveram 2,6 vezes mais chance de parassonias em relação àquelas que consumiram alimentos não estimulantes. Não houve diferença entre os grupos em relação ao tipo de alimento (p = 0,78) ou horário da última refeição antes de ir para a cama (p = 0,50). Conclusão Nossos achados sugerem que a ingestão de alimentos estimulantes está associada com o desenvolvimento de parassonias em crianças.

Sleep-related disturbances among adolescents with cancer: a systematic review.

UNLABELLED: The purpose of this systematic review was to examine the evidence for sleep-related disturbances among adolescents with cancer, particularly the types of disturbances reported, using single and mixed paediatric oncology samples. METHODS: Electronic searches of Medline, PubMed, and the Cochrane Database of Systematic Reviews since inception to September 2013 were conducted to identify all relevant studies. Search terms included sleep, a second term including adolescent, juvenile, youth, child, or childhood, and a third term including cancer, leukaemia, or brain tumour. A total of 41 articles met inclusion criteria and were included in the review. Of these, 32 included patients with leukaemia and 21 included patients with brain tumours. Sleep-related disturbances included difficulty initiating sleep, fragmented sleep, disordered breathing, parasomnias, napping, daytime sleepiness/fatigue, and unspecified disturbances. Adolescents with cancer experience many problems related to sleep. Given the increase in survival rates of the youth diagnosed with leukaemia or brain tumours, symptom management is an essential area of research in order to continue improving quality of life.

Sleep disorders in children with traumatic brain injury: a case of serious neglect.

AIM: The aim of this study was to review the basic aspects of sleep disturbance in children with traumatic brain injury (TBI). METHOD: A search was performed on reports of sleep disturbances in children who had suffered TBI. Adults with TBI were also considered to anticipate the nature and significance of such disturbances in younger patients. Types of reported sleep disturbance were noted and their possible aetiology and management considered. RESULTS: Sleep disturbance has consistently been associated with TBI but the literature suggests that this aspect of patient care is often inadequately considered and there has been little research on the subject, especially in relation to children. Excessive daytime sleepiness is often mentioned, less so insomnia and parasomnias, but there is little information about the specific sleep disorders underlying these problems. INTERPRETATION: Sleep disorders with potentially important developmental consequences have been neglected in the care of children with TBI. Screening for sleep problems should be routine and followed, if indicated, by a detailed diagnosis of the child's underlying specific sleep disorder, the possible aetiology of which includes neuropathology and potential medical, psychological, or psychiatric comorbidities. Appropriate assessments and modern treatment options are now well defined although generally underutilized. Further well-designed research is needed for which guidelines are available.

Progesterone for hot flush and night sweat treatment--effectiveness for severe vasomotor symptoms and lack of withdrawal rebound.

A controlled trial recently showed that oral micronized progesterone (Progesterone, 300 mg at h.s. daily) was effective for vasomotor symptoms (VMS) in 133 healthy early postmenopausal women. Here, we present subgroup data in women with severe VMS (50 VMS of moderate-severe intensity/wk) and also 1-mo withdrawal study outcomes. Women with severe VMS (n = 46) resembled the full cohort but experienced 10 VMS/d of 3 of 4 intensity. On therapy, the progesterone VMS number (#) decreased significantly more than placebo # to 5.5/day (d) versus 8/d (ANCOVA -2.0 95% CI: -3.5 to -0.4). Just after trial mid-point, a withdrawal substudy (D/C) was added--56 women were invited and 34 (61%) took part (progesterone 17; placebo 17). Those in the D/C cohort resembled the whole cohort. On stopping, VMS gradually increased--at D/C week 4, on progesterone, VMS daily # reached 78% and significantly less than baseline (-3.0 to -0.8) but placebo VMS # did not differ from run-in. In summary, progesterone is effective for severe VMS and does not cause a rebound increase in VMS when stopped. That progesterone may be used alone for severe VMS and unlike estrogen does not appear to cause a withdrawal rebound increases VMS treatment options.

Relação entre epilepsia e sono: clínica e fisiopatogenia / Relationship between epilepsy and sleep: clinical symptoms and physiopathogeny

Introdução: A relação entre sono e epilepsia é relevante clinico-epidemiologicamente e de conhecimento antigo, apesar da sua fisiopatogeniaprecisar ser melhor esclarecida. Objetivos: Reconhecer: a influência do sono na expressão clinico-eletroencefalografica da epilepsia e vice-versa;transtornos do sono mais comumente encontrados em pacientes com epilepsia e de diagnóstica diferencial dificultado; influência das drogas antiepilépticas (DAE) no sono. Métodos: Revisão narrativa principalmente com base na busca no Pubmed de artigos publicados nos últimoscinco anos com os termos epilepsy e sleep no título, revisões. Resultados: Existem síndromes epilépticas mais relacionadas ao sono-vigília ,como: epilepsia noturna do lobo frontal; epilepsia benigna da infância com pontas centrotemporais; epilepsia com ponta-onda continua durante o sono de ondas lentas e síndrome de Landau-Kleffner; epilepsia do lobo temporal (generalização secundária); síndromes de West e de Lennox-Gastaut; epilepsias idiopáticas generalizadas, principalmente crises generalizadas tônico-clônicas do despertar, mas, também, epilepsia mioclônicajuvenil. Os transtornos do sono que mais acometem os pacientes com epilepsia são: sonolência diurna excessiva, insônia e síndrome da apneiaobstrutiva do sono. A diferenciação de epilepsia noturna do lobo frontal deve ser feita principalmente com transtornos do despertar do sono não REM e outras parassonias. As DAE podem modificar a arquitetura do sono e o ciclo sono-vigília. Algumas das novas DAE podem ter efeito mais favorável na profundidade e continuidade do sono do que as antigas. O ciclo do sono-vigília é regulado através de vários intervenientes quetambém podem afetar a expressão da epilepsia: estruturas anatômicas, neurotransmissores ou eventos expressos no EEG que podem serproconvulsivantes ou anticonvulsivantes.

Introduction: The relationship between sleep and epilepsy is important clinically and epidemiologically, and of old knowledge, althoughits physiopathogeny needs to be better explained. Objective: To recognize: the influence of the sleep in the epilepsy clinical-electroencephalographicexpression, and vice versa; sleep disorders more commonly found in patients with epilepsy and of more difficult differential diagnosis; influence of the antiepileptic drugs (AED) in the sleep. Methods: Narrative review mainly based in the articles obtained by the search in the Pubmed published in the last five years with the terms epilepsy and sleep in the title, reviews. Results: Epileptic syndromes more related to the sleep period: nocturnal frontal lobe epilepsy; benign childhood epilepsy with centrotemporal spikes; epilepsy with continuous spike-and-wave dischargesduring slow-wave sleep and Landau-Kleffner syndrome; temporal lobe epilepsy (secondary generalization); West and Lennox-Gastaut syndromes; idiopathic generalized epilepsy, mainly epilepsy with generalized tonic-clonic on awakening, but, also, juvenile myoclonic epilepsy. The sleep disorders that more frequently occurs in patients with epilepsy are excessive daytime sleepiness, insomnia and obstructive sleep apnea syndrome. The differentiation of nocturnal frontal lobe epilepsy should be mainly made with the non REM sleep disorders of the awakening and others parasomnias. AED can modify the architecture of the sleep and the sleep-wake cycle. Some of new AED can have more favorable effect in the depth and continuity of the sleep than the old ones. The sleep-wake cycle is regulated through several interveners that may affect the expressionof the epilepsy: anatomical structures, neurotransmitters or events expressed in EEG that can be proconvulsant or anticonvulsant.

Insulinoma presenting itself as a night paroxysmal disorder with spontaneous recovery.

A 64-year-old woman with night paroxysmal episodes is described. Her symptoms began 9 months ago with attacks of bizarre movement, which were always present in the second part of the night. She had no attacks during the daytime. Her husband reported confusion and disorientation followed by long periods of unresponsiveness. The patient underwent a night polysomnography recording. Around 4 o'clock in the morning bizarre movements with stereotypic behaviour appeared. She was rolling her head from side to side, moaning, and stretching her limbs. These periods first lasted for minutes, and were constantly repeated during the night. EEG findings suggested metabolic encephalopathy. At that time finger prick test revealed a profound hypoglycaemia (1.2 mmol/l), high insulin (200 pmol/l), and C-peptide (6.63 nmol/l). Ultrasonography and MRI confirmed the insulinoma in the head of the pancreas. To our knowledge our case is the first patient with insulinoma attacks only during sleep time.

Compensatory rebound of body movements during sleep, after asphyxia in neonatal rats / Resposta compensatória dos movimentos corporais do sono após a asfixia em ratos recém-nascidos

PURPOSE: The usefulness of body movements that occur during sleep when assessing perinatal asphyxia and predicting its long-term consequences is contradictory. This study investigated whether neonatal rats manifest these movements in compensatory rebound after asphyxia, and if these alterations play an important role in its pathogenesis. METHODS: Eight neonatal rats (aged 6-48h) were implanted with small EMG and EKG electrodes and sleep movements were recorded over a 30-minute control period. Recordings were continued during asphyxia caused by the enclosure of the animal in a polyvinyl sheet for 60 minutes, followed by a 30-minute recovery period. RESULTS: Heart rate was lowered to bradycardic level during asphyxia causing behavioral agitation and increased waking time during the initial phase (30 minutes). Sleep-related movements were also significantly reduced from 12.5 ± 0.5 (median ± SE/2min) to 9.0 ± 0.44 in the final half of the period (Anova, p<0.05). Movement frequency increased in the recovery period to 15.0 ± 0.49 (Anova, p<0.05). CONCLUSION: These data show that newborn rats present compensatory rebound of body movements during sleep which may help in the diagnosis of asphyxia and other problems related to sleep parameters.

OBJETIVO: A utilidade dos movimentos corporais (MC) que ocorrem durante o sono para diagnosticar e predizer as conseqüências, em longo prazo, da asfixia perinatal é contraditório. Este estudo investigou se ratos recém-nascidos (RN) manifestam MC em resposta compensatória à asfixia, e se estas alterações podem ter alguma importância na sua patogênese. MÉTODOS: Oito ratos RN (6-48h de vida) foram submetidos à implantação de pequenos eletrodos para registros da eletromiografia e eletrocardiografia. Os MC e a freqüência cardíaca (FC) foram registrados durante períodos de 30 min: fase controle (F1), fases de asfixia (F2; F3) e fase de recuperação pós-asfixia (F4). A asfixia foi promovida pelo envolvimento completo do animal com uma lâmina de polivinil. RESULTADOS: A FC diminuiu progressivamente durante F2 e F3 até a bradicardia. Em F2 houve grande agitação dos animais e aumento dos períodos de vigília. Em F3 houve redução significante dos MC de 12,5 ± 0,5 (Md ± SE/2min) para 9,0 ± 0,44 (P<0,05). A freqüência dos MC aumentou em F4 para 15,0 ± 0,49. CONCLUSÃO: Estes dados mostram que ratos RN com asfixia apresentam MC compensatórios durante o sono que podem ajudar no diagnóstico desta afecção e de outros problemas relacionados aos parâmetros do sono.

Catathrenia: parasomnia or uncommon feature of sleep disordered breathing?

OBJECTIVE: We report a series of seven consecutive cases of catathrenia (sleep related groaning) that differ from limited previous reports in the literature with regard to sleep stage and response to treatment. BACKGROUND: Catathrenia was recently defined as a parasomnia in the International Classification of Sleep Disorders Diagnostic and Coding Manual (ICSD-2), but there is debate about its classification, and its response to CPAP is unknown. METHODS: We present 7 consecutive patients presenting with catathrenia over a 5-year period. They were all young women, ranging in age from 20 to 34 years with a body mass index (BMI) <25. They underwent standard clinical evaluation, questionnaires, physical exam, craniofacial evaluations, and nocturnal polysomnography. All seven were titrated on continuous passive airway pressure (CPAP) treatment for sleep disordered breathing then offered surgical treatment if unable to tolerate or adhere to CPAP recommendations. RESULTS: Groaning was present throughout all stages of sleep. The mean (SD) AHI and RDI were 3.2 (0.56) and 13.1 (2.4) respectively. CPAP resolved groaning in all cases. 5 patients (71%) elected subsequent surgical intervention. Three of the 4 that followed up after surgery required adjuvant oral appliance treatment, but all four ultimately had resolution of groaning. CONCLUSIONS: Catathrenia may have subtypes related to sleep stage specificity or presence of sleep disordered breathing. In our heterogeneous group of non-obese women with a normal AHI and elevated RDI, CPAP and select soft tissue surgeries of the upper airway (often augmented with an oral appliance) successfully treated nocturnal groaning.

Children with autism: effect of iron supplementation on sleep and ferritin.

To determine if there is a relationship between low serum ferritin and sleep disturbance in children with autism spectrum disorder, an 8-week open-label treatment trial with oral iron supplementation was conducted as a pilot study. At baseline and posttreatment visits, parents completed a Sleep Disturbance Scale for Children and a Food Record. Blood samples were obtained. Thirty-three children completed the study. Seventy-seven percent had restless sleep at baseline, which improved significantly with iron therapy, suggesting a relationship between sleep disturbance and iron deficiency in children with autism spectrum disorder. Sixty-nine percent of preschoolers and 35% of school-aged children had insufficient dietary iron intake. Mean ferritin increased significantly (16 microg/L to 29 microg/L), as did mean corpuscular volume and hemoglobin, suggesting that low ferritin in this patient group resulted from insufficient iron intake. Similar prevalence of low ferritin at school age as preschool age indicates that children with autism spectrum disorder require ongoing screening for iron deficiency.

[Sleep disorders in infancy--aspects of diagnosis and somatic background]. / Schlafstörungen im Kleinkindesalter--Diagnostik, Differenzialdiagnostik und somatische Hintergründe.

Sleep-related disturbed breathing and parasomnia in very young children are in the focus of epidemiological interest. The cardinal symptom, i.e. snoring, in connection with nocturnal perspiration, mouth breathing, susceptibility to infection of the upper respiratory tract and tiredness during the day or hypermotility, can be an indication of obstructive sleep apnea (OSA). The common treatment is adenotomy unless there is indication of allergic swelling of the nasal mucous membrane. Other anatomic predispositions for OSA must be considered (tonsillar hypertrophy, midfacial hypoplasia, micro- and retrognathia, e.g. in patients with Down's syndrome or patients with preoperated cleft lip face palate). Inhalative nasal corticoids are a possible alternative to adenotomy in light to medium grade cases of OSA. Tonsillotomy is indicated only in serious OSA cases, tonsillectomy is only justified in cases of chronic tonsillitis or more than 4-6 cases of angina in the last 12 months. Treatment with nasal CPAP is tolerated well also in childhood. Patients with central hypoventilation syndromes, insufficiency of the respiratory musculature or obesitas hypoventilation syndrome can usually be ventilated by non-invasive approach using a nasal mask. Patients suffering from parasomnia should always be asked if they snore at night because if OSA is diagnosed and treated, there are very good prospects of curing somnambulism as well. Like with narcolepsy and REM sleep, a close HLA association has also been identified for family somnambulism. In cases of parasomnia which becomes manifest only after very young age frontal lobe epilepsy should be suspected and searched by polysomnographic and simultaneous continuous nocturnal video surveillance. If reversive development or unclear motoric and utterance phenomena are observed, sleep-bound convulsive disorder should be looked for. Syncopal events can require comprehensive cardiological diagnosis, including exclusion of nightly disorders of the cardiac rhythm.