A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study.

BACKGROUND: Autoimmunity might be associated with or implicated in sleep and neurodegenerative disorders. We aimed to describe the features of a novel neurological syndrome associated with prominent sleep dysfunction and antibodies to a neuronal antigen. METHODS: In this observational study, we used clinical and video polysomnography to identify a novel sleep disorder in three patients referred to the Sleep Unit of Hospital Clinic, University of Barcelona, Spain, for abnormal sleep behaviours and obstructive sleep apnoea. These patients had antibodies against a neuronal surface antigen, which were also present in five additional patients referred to our laboratory for antibody studies. These five patients had been assessed with polysomnography, which was done in our sleep unit in one patient and the recording reviewed in a second patient. Two patients underwent post-mortem brain examination. Immunoprecipitation and mass spectrometry were used to characterise the antigen and develop an assay for antibody testing. Serum or CSF from 298 patients with neurodegenerative, sleep, or autoimmune disorders served as control samples. FINDINGS: All eight patients (five women; median age at disease onset 59 years [range 52-76]) had abnormal sleep movements and behaviours and obstructive sleep apnoea, as confirmed by polysomnography. Six patients had chronic progression with a median duration from symptom onset to death or last visit of 5 years (range 2-12); in four the sleep disorder was the initial and most prominent feature, and in two it was preceded by gait instability followed by dysarthria, dysphagia, ataxia, or chorea. Two patients had a rapid progression with disequilibrium, dysarthria, dysphagia, and central hypoventilation, and died 2 months and 6 months, respectively, after symptom onset. In five of five patients, video polysomnography showed features of obstructive sleep apnoea, stridor, and abnormal sleep architecture (undifferentiated non-rapid-eye-movement [non-REM] sleep or poorly structured stage N2, simple movements and finalistic behaviours, normalisation of non-REM sleep by the end of the night, and, in the four patients with REM sleep recorded, REM sleep behaviour disorder). Four of four patients had HLA-DRB1*1001 and HLA-DQB1*0501 alleles. All patients had antibodies (mainly IgG4) against IgLON5, a neuronal cell adhesion molecule. Only one of the 298 controls, who had progressive supranuclear palsy, had IgLON5 antibodies. Neuropathology showed neuronal loss and extensive deposits of hyperphosphorylated tau mainly involving the tegmentum of the brainstem and hypothalamus in the two patients studied. INTERPRETATION: IgLON5 antibodies identify a unique non-REM and REM parasomnia with sleep breathing dysfunction and pathological features suggesting a tauopathy. FUNDING: Fondo de Investigaciones Sanitarias, Centros de Investigación Biomédica en Red de enfermedades neurodegenerativas (CIBERNED) and Respiratorias (CIBERES), Ministerio de Economía y Competitividad, Fundació la Marató TV3, and the National Institutes of Health.

Trastornos y hábitos de sueño en niños y adolescentes con autismo / Sleep habits and disorders in children and adolescents

Existe una alta prevalencia de trastornos del sueño en personas con autismo. El propósito de este estudio fue describir las alteraciones del sueño y malos hábitos de sueño en una población de niños y adolescentes con autismo y determinar si existen diferencias según la edad. Estudio transversal, descriptivo. Se incluyeron 14 niños y 12 adolescentes con autismo procedentes del Centro de Atención Integrada para personas con Autismo en San Cristóbal, Venezuela. Fueron evaluados con un cuestionario para padres, que registra los hábitos de sueño en un periodo de 6 meses. Se establecieron comparaciones entre niños menores de 12 años y adolescentes. El trastorno de sueño informado con mayor frecuencia en niños fue dificultad para quedarse dormido (35,7%) y en adolescentes enuresis (30%). En cuanto a malos hábitos de sueño, predominó en niños, la necesidad de estar acompañado al momento de quedarse dormido (64,3%) al igual que en los adolescentes (33,3%). En Venezuela, un alto porcentaje de niños y adolescentes con autismo presentan alteraciones del sueño superiores a la población general; tales como dormir en cama de los padres o necesitar compañía al momento de quedarse dormidos; sin embargo, muchos padres no consideran que esto sea un problema serio que afecte a la familia o al niño.

There is a high prevalence of sleep disorders in people with autism. The objective of this study was to describe sleep disturbances and poor sleep habits in a population of children and adolescents with autism in Venezuela and to determine differences by age. Descriptive, crosssectional study. 14 children and 12 adolescents with autism were assessed with a questionnaire for parents, which recorded the sleep habits from 6 months earlier in the Center of integrated care for people with autism, in San Cristobal, Venezuela. Comparisons were established between children under 12 years old and adolescents. The sleep disorder reported more frequently in children was difficulty falling asleep (35.7%) and enuresis in adolescents (30%). In regard to bad sleep habits, the need to be accompanied at the time of falling asleep predominated in children (64.3%), as well as in adolescents (33.3%). In Venezuela, a high percentage of children and adolescents with autism have more sleep disorders than the general population, as the need to sleep in parent’s bed and the need of company when falling asleep. However, many parents do not considerthis as a serious problem affecting the family or the child.

Rhythmic tongue movements during sleep: a peculiar parasomnia in Costello syndrome.

We describe a peculiar parasomnia observed in four Costello infants, characterized by periodic rhythmic movements of the tongue. Ten Costello patients (4 male; age range 9 months to 29 years) underwent 1 full-night laboratory-based video polysomnography. The four youngest patients (2 male and 2 female; age range 9-31 months) presented during sleep repeated stereotyped movements of the tongue, producing a sucking-like or licking-like movement, mostly during non-rapid eye movement (NREM) sleep. Rhythmic tongue movements in Costello syndrome show the features of an NREM sleep parasomnia. Tongue movements during sleep probably originate from brainstem structures and could be facilitated by an impaired control of the oropharyngeal and tongue muscles.

Parasomnias decline during pregnancy.

OBJECTIVES: A survey of the effects of pregnancy on parasomnias. MATERIAL AND METHODS: In an area of a central hospital and the maternity care units in the nearby rural community, women were interviewed during and after their pregnancy with a series of five questionnaires to assess the frequency of their parasomnias. The first questionnaire covered the 3 months before becoming pregnant, the next three the trimesters of pregnancy and the last one the 3 months after delivery. Altogether 325 mothers filled all the five questionnaires and constitute the study group. RESULTS: The total number of parasomnias declined (P < 0.001) during pregnancy and even more among the primiparas than among the multiparas (difference until third trimester, P=0.02). Among various parasomnias reported, sleep talking and sleepwalking decreased from the prepregnant period to the second trimester (22.8 vs 12.6%, change P=0.003), and the reported sleep starts also diminished from the prepregnant time to the first trimester (78.5 vs 63.1%, P < 0.001), but these phenomena did not change further during the follow-up. Altogether 55.7% of the women reported having nightmares 3 months before the pregnancy, and 47.7, 49.5, 41.2 and 40.3% (change from the prepregnant period, P < 0.001), respectively, at first, second and third trimester and after the delivery. Reported hypnagogic hallucinations decreased from the prepregnant time to the first trimester (9.8 vs 6.5%, P=0.027), but returned thereafter to the previous level. During the prepregnant period, 25.8% of the women reported bruxism and only 19.9% during the first trimester (P=0.009). Though the prevalence of sleep paralysis decreased during the first trimester of pregnancy, it was the only parasomnia that increased during later pregnancy (from 5.7 to 13.3% in the second trimester, P < 0.013). CONCLUSIONS: The reported frequency of most parasomnias decreases during pregnancy and even more in primiparas than multiparas.

Parasomnias--an update.

Primary parasomnias are a group of sleep-related clinical disorders that occur in otherwise healthy children, which may be provoked by a variety of physical, psychosocial, and environmental stimuli. In typical cases, additional investigations are not necessary, and treatment should be instituted with the aim of reducing the frequency and adverse consequences of the parasomnia. In patients with co-existing clinical disorders, parasomnias need to be distinguished from symptoms of the underlying disorder. This article provides a brief review of the recent literature regarding parasomnias, and a clinically oriented approach to the management of parasomnias in patients with co-existing clinical disorders.