Narcolepsy with Cataplexy Associated with Nocturnal Compulsive Behaviors: A Case-Control Study

NARCOLEPSY WITH CATAPLEXY AND NOCTURNAL COMPULSIVE BEHAVIORS doi: 10.5665/sleep.1280 Narcolepsy with Cataplexy Associated with Nocturnal Compulsive Behaviors: A Case-Control Study Vincenzo Palaia, MD1; Francesca Poli, MD, PhD1; Fabio Pizza, MD1; Elena Antelmi, MD1; Christian Franceschini, PsyD, PhD1; Keivan Kaveh Moghadam, MD1; Frederica Provini, MD, PhD1; Uberto Pagotto, MD2; Pasquale Montagna, MD1†; Carlos H. Schenck, MD3; Emmanuel Mignot, MD4; Giuseppe Plazzi, MD1 1 Department of Neurological Sciences University of Bologna, Bologna, Italy; 2Endocrinology Unit and Centre of Applied Biomedical Research, Department of Clinical Medicine, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Italy; 3Minnesota Regional Sleep Disorders Center, Department of Psychiatry, Hennepin County Medical Center, University of Minnesota Medical School, Minneapolis, MN; 4Center for Narcolepsy, Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA Study Objectives: To assess the prevalence of sleep related-eating disorder (SRED) and nocturnal smoking (NS) in patients with narcolepsy with cataplexy (NC). Design: Case-control study. Setting: University hospital. Patients or Participants: 65 consecutive adult NC patients (33 men; mean age 43.9 ± 19.2 years) and 65 age-, sex-, and geographical originmatched controls. Interventions: Validated questionnaires were used to investigate SRED, NS, restless legs syndrome (RLS), and psychopathological traits (using Eating Disorder Inventory-2 [EDI-2]; Maudsley Obsessive-Compulsive Inventory [MOCI]; and Beck Depression Inventory [BDI]). Measurements and Results: NC patients showed a higher prevalence of SRED (32% vs 3%, P = 0.00001), NS (21% vs 0%, P = 0.00006), and RLS (18% vs 5%, P = 0.013) than controls. Moreover, NC patients presented more frequently with an eating-related pathological profile on the EDI-2 (80% vs 46%, P = 0.00006) and had a higher prevalence of depressed mood on the BDI (41% vs 18%, P = 0.004). In comparison to patients without SRED, NC patients with SRED were more frequently women (71% vs 39%, P = 0.013), had higher “bulimic” (29% vs 2%, P = 0.004) and “social insecurity” (48% vs 18%, P = 0.013) traits on the EDI-2, had higher obsessive-compulsiveness on the MOCI (29% vs 4%, P = 0.009), and were more depressed on the BDI (67% vs 29%, P = 0.005). NC patients with NS showed more frequent pathological profiles on the EDI-2 (100% vs 75%, P = 0.035), including the “bulimic” (29% vs 6%, P = 0.015), “perfectionism” (43% vs 14%, P = 0.016), and “social insecurity” (50% vs 22, P = 0.035) profiles. Conclusion: Our study shows a strong association of the compulsive nocturnal behaviors SRED and NS with adult NC. Keywords: Narcolepsy with cataplexy, nocturnal compulsive behaviors, case-control study, sleep related-eating disorder, nocturnal smoking. Citation: Palaia V; Poli F; Pizza F; Antelmi E; Franceschini C; Moghadam KK; Provini F; Pagotto U; Montagna P; Schenck CH; Mignot E; Plazzi G. Narcolepsy with cataplexy associated with nocturnal compulsive behaviors: a case-control study. SLEEP 2011;34(10):1365-1371. INTRODUCTION Narcolepsy with cataplexy (NC) is a central nervous system hypersomnia, characterized by excessive daytime sleepiness (EDS), cataplexy (transient loss of muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations, and disrupted nocturnal sleep.1 It is caused by the selective loss of hypothalamic neurons2 producing hypocretin-1 and 2 (or orexin-A and B),3,4 two related peptides involved in regulation of sleep-wake transition, energy homeostasis, feeding behavior, and reward systems.5 Accordingly, low/undetectable cerebrospinal (CSF) hypocretin-1 (hrct-1) is observed in almost all cases of NC. Sleep-related eating disorder (SRED) is a NREM parasomnia, characterized by recurrent episodes of involuntary eating and drinking during arousals from the main sleep period. It involves nocturnal consumption of food or toxic substances, dis† Dr. Montagna died December 9, 2010. Submitted for publication December, 2010 Submitted in final revised form May, 2011 Accepted for publication May, 2011 Address correspondence to: Giuseppe Plazzi, Dipartimento di Scienze Neurologiche dell’Università di Bologna, via Ugo Foscolo, 7, 40123 Bologna, Italy; Tel: +390512092926; Fax: +390512092963; E-mail: giuseppe. SLEEP, Vol. 34, No. 10, 2011 1365 ruption of nocturnal sleep, and increased risk for sleep-related injuries including those derived from food seeking/cooking, morning anorexia, or other medical consequences.1 SRED has been found associated with various sleep disorders in case series: sleepwalking (SW), periodic limb movements during sleep (PLMS), narcolepsy, restless legs syndrome (RLS), and obstructive sleep apnea (OSA).6,7 The high rate of PLMS and rhythmic masticatory muscle activity in SRED patients,8 together with the high prevalence of SRED (33%) in idiopathic RLS,9 suggests a pathophysiological derangement of the dopaminergic system. Besides SRED, other compulsive behaviors can arise from nocturnal sleep, such as nocturnal smoking (NS). NS is an “out of control” smoking behavior during nocturnal awakenings characterized by an inner desire to smoke associated or not associated with eating. NS has also been reported in RLS patients,10 a frequent and possibly confounding condition in NC.11 Finally, NC has been associated with excessive weight gain and obesity via unclear mechanisms.12-18 Some studies have suggested a common genetic predisposition,19 while other authors have found that increased BMI is intrinsic to the NC phenotype.18 In this context, weight gain occurs despite paradoxically lowered daytime caloric intake, suggesting decreased energy expenditure.18 Given the frequent association of SRED with other sleep disorders and the recent report of food craving-behaviors in NC,20,21 our study aimed at assessing the prevalence of SRED and NS in Nocturnal Compulsive Behaviors in Narcolepsy—Palaia et al adult NC patients. We hypothesized that these abnormalities could contribute to obesity in NC. PATIENTS AND METHODS Patients Sixty-five consecutive patients with a clinical and polysomnographic diagnosis of NC according to the International Classification of Sleep Disorders (ICSD-2)1 were enrolled in this study. These subjects were consecutive patients routinely followed at the Outpatient Clinic for Narcolepsy, Department of Neurological Sciences, University of Bologna between January 2008 and April 2009. Each patient was asked to indicate an acquaintance (not relative) of the same sex, age (± 3 years), and geographical area of origin (Northern, Central, or Southern Italy) who was willing to complete the same questionnaires. The institutional review board of the Department of Neurological Sciences, University of Bologna approved the study project, and all subjects signed a written informed consent. Table 1—NC patients vs Controls Number of subjects (N) Demog (...truncated)