Original Article Sleep architecture in infants with spinal muscular atrophy type 1 Elisabetta Verrillo a, *, Oliviero Bruni b , Martino Pavone a , Raffaele Ferri c , Valeria Caldarelli a , Luana Novelli b , Maria Beatrice Chiarini Testa a , Renato Cutrera a a Respiratory Unit, Pediatric Department, Bambino Gesù Children’s Research Hospital, Rome, Italy b Department of Developmental and Social Psychology, Sapienza University, Rome, Italy c Department of Neurology, Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Italy A R T I C L E I N FO Article history: Received 31 January 2014 Received in revised form 28 April 2014 Accepted 29 May 2014 Available online 2 July 2014 Keywords: Spinal muscular atrophy type 1 Sleep Cyclic alternating pattern Sleep breathing disorder Central nervous system Arousability A B ST R AC T Objective: Few reports on sleep patterns of patients with spinal muscular atrophy type 1 (SMA1) have been published and none on sleep microstructure. The aim of this study was to analyze sleep architec- ture and microstructure in a group of infants with SMA1, compared with age- and sex-matched controls. Methods: Twelve SMA1 patients (six males, mean age 5.9 months) and 10 controls (five males, mean age 4.8 months) underwent full polysomnography to evaluate their sleep architecture and microstructure by means of the cyclic alternating pattern (CAP). Results: Compared with control children, SMA1 patients showed increased sleep latency and apnea/ hypopnea index. CAP analysis revealed a significant increase in the percentage of A1 CAP subtypes, a re- duction of that of A3 subtypes and of A2 and A3 indexes (number/h), indicating a dysfunction of the arousal system in these patients. Conclusion: The results indicate the presence of an abnormality of sleep microstructure in SMA1 pa- tients, characterized by a reduction of A2 and A3 CAP subtypes. We hypothesize that SMA1 patients have reduced arousability during non-rapid eye movement sleep, which could be interpreted as additional evidence of central nervous system involvement in this disease. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Spinal muscular atrophy (SMA) is an autosomal recessive dis- order characterized by degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem [1]. It has an estimated incidence of 1 in 6000 to 1 in 10,000 live births and with a carrier frequency of 1 in 40 to 1 in 60 [2,3]. The gene re- sponsible for SMA has been located within the complex genomic region at chromosome 5q11.2–q13.3, which contains a 500 kb in- verted duplication [4,5]. The phenotype expression of the disease, inversely proportion- al to the amount of complete survival motor neuron 1 (SMN1) protein, ranges from severe generalized paralysis and need for ven- tilatory support from birth to relatively mild conditions present- ing in young adults. However, SMA type 1 (SMA1) is a very severe condition in which the affected infant never attains the ability to sit independently, is affected by severe chest infections with acute respiratory failure, and usually dies before the second birthday [6,7]. Sleep breathing disorders are an additional cause of morbidity and impaired quality of life in these children who have been re- ported to present with significantly more sleep apnea and thoraco- abdominal asynchrony during the inspiratory and expiratory phases of both quiet and active sleep [8]. There are very few studies of sleep patterns in patients with SMA, and especially in subjects with SMA1 [9]. In a polysom- nographic (PSG) study of 32 neuromuscular patients, four with a form of SMA sleep architecture revealed an increase in stage 1 sleep coupled with a decrease or absence of rapid eye movement (REM) sleep [10]. Another study on seven SMA children (six with SMA type 1.5– 1.8, 1 with SMA type 2) showed impaired sleep architecture, but compensated nocturnal and diurnal gas exchange; in these cases, nocturnal non-invasive ventilation (NIV) resulted in a significant im- provement of sleep architecture with higher sleep efficiency, de- creased light sleep counterbalanced by increased deep sleep, longer REM sleep, and significantly fewer electroencephalographic (EEG) arousals [11]. All these previous studies only evaluated sleep stage architec- ture, and, to the best of our knowledge, no current studies have * Corresponding author at: Bambino Gesù Pediatric Hospital and Research Institute, Piazza Sant’Onofrio 4, 00165 Rome, Italy. Tel.: +39 066 8592 009; fax: +39 066 8592 300. E-mail address: elisabettaverrillo@hotmail.com (E. Verrillo). http://dx.doi.org/10.1016/j.sleep.2014.05.029 1389-9457/© 2014 Elsevier B.V. All rights reserved. Sleep Medicine 15 (2014) 1246–1250 Contents lists available at ScienceDirect Sleep Medicine journal homepage: www.elsevier.com/locate/sleep