Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Neurological Sciences
Published in: Neurological Sciences 3/2019

Open Access 01-03-2019 | Review Article

Red Flags for early referral of people with symptoms suggestive of narcolepsy: a report from a national multidisciplinary panel

Authors: L. Vignatelli, E. Antelmi, I. Ceretelli, M. Bellini, C. Carta, P. Cortelli, L. Ferini-Strambi, R. Ferri, R. Guerrini, F. Ingravallo, V. Marchiani, F. Mari, G. Pieroni, F. Pizza, M. C. Verga, E. Verrillo, D. Taruscio, Giuseppe Plazzi

Published in: Neurological Sciences | Issue 3/2019

Login to get access

Abstract

Objective

Narcolepsy is a lifelong disease, manifesting with excessive daytime sleepiness and cataplexy, arising between childhood and young adulthood. The diagnosis is typically made after a long delay that burdens the disease severity. The aim of the project, promoted by the “Associazione Italiana Narcolettici e Ipersonni” is to develop Red Flags to detect symptoms for early referral, targeting non-sleep medicine specialists, general practitioners, and pediatricians.

Materials and methods

A multidisciplinary panel, including patients, public institutions, and representatives of national scientific societies of specialties possibly involved in the diagnostic process of suspected narcolepsy, was convened. The project was accomplished in three phases. Phase 1: Sleep experts shaped clinical pictures of narcolepsy in pediatric and adult patients. On the basis of these pictures, Red Flags were drafted. Phase 2: Representatives of the scientific societies and patients filled in a form to identify barriers to the diagnosis of narcolepsy. Phase 3: The panel produced suggestions for the implementation of Red Flags.

Results

Red Flags were produced representing three clinical pictures of narcolepsy in pediatric patients ((1) usual sleep symptoms, (2) unusual sleep symptoms, (3) endocrinological signs) and two in adult patients ((1) usual sleep symptoms, (2) unusual sleep symptoms). Inadequate knowledge of symptoms at onset by medical doctors turned out to be the main reported barrier to diagnosis.

Conclusions

This report will hopefully enhance knowledge and awareness of narcolepsy among non-specialists in sleep medicine in order to reduce the diagnostic delay that burdens patients in Italy. Similar initiatives could be promoted across Europe.
Appendix
Available only for authorised users
Literature
1.
American Academy of Sleep Medicine (2005) The International Classification of Sleep Disorders: Diagnostic & Coding Manual. 2nd ed. Rochester, MN: American Academy of Sleep Medicine
2.
3.
Postiglione E, Antelmi E, Pizza F, Lecendreux M, Dauvilliers Y, Plazzi G (2018) The clinical spectrum of childhood narcolepsy. Sleep Med Rev 38:70–85CrossRefPubMed
4.
Dauvilliers Y, Montplaisir J, Molinari N, Carlander B, Ondze B, Besset A, Billiard M (2001) Age at onset of narcolepsy in two large populations of patients in France and Quebec. Neurology 57:2029–2033CrossRefPubMed
5.
Hublin C, Partinen M, Kaprio J, Koskenvuo M, Guilleminault C (1994) Epidemiology of narcolepsy. Sleep 17:S7–12
6.
Ohayon MM, Priest RG, Zulley J, Smirne S, Paiva T (2002) Prevalence of narcolepsy symptomatology and diagnosis in the European general population. Neurology 58:1826–1833CrossRefPubMed
7.
Silber MH, Krahn LE, Olson EJ, Pankratz VS (2002) The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study. Sleep 25:197–202CrossRefPubMed
8.
Wing YK, Li RH, Lam CW, Ho CK, Fong SY, Leung T (2002) The prevalence of narcolepsy among Chinese in Hong Kong. Ann Neurol 51:578–584CrossRefPubMed
9.
Longstreth WT Jr, Koepsell TD, Ton TG, Hendrickson AF, van Belle G (2007) The epidemiology of narcolepsy. Sleep 30:13–26CrossRefPubMed
10.
Shin YK, Yoon IY, Han EK, No YM, Hong MC, Yun YD, Jung BK, Chung SH, Choi JB, Cyn JG, Lee YJ, Hong SC (2008) Prevalence of narcolepsy-cataplexy in Korean adolescents. Acta Neurol Scand 117:273–278CrossRefPubMed
11.
Wijnans L, Lecomte C, de Vries C, Weibel D, Sammon C, Hviid A, Svanström H, Mølgaard-Nielsen D, Heijbel H, Dahlström LA, Hallgren J, Sparen P, Jennum P, Mosseveld M, Schuemie M, van der Maas N, Partinen M, Romio S, Trotta F, Santuccio C, Menna A, Plazzi G, Moghadam KK, Ferro S, Lammers GJ, Overeem S, Johansen K, Kramarz P, Bonhoeffer J, Sturkenboom MCJM (2013) The incidence of narcolepsy in Europe: before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns. Vaccine 31:1246–1254CrossRefPubMed
12.
Taruscio D, Rocchetti A, Torreri P, Ferrari G, Kodra Y, Salerno P, Vittozzi L (2017). Il Registro Nazionale Malattie Rare nel contesto nazionale e internazionale. 3° Rapporto (dati al 31 dicembre 2014). Roma: Istituto Superiore di Sanità. (Rapporti ISTISAN 17/8)
13.
Taruscio D, Vittozzi L, Rocchetti A, Torreri P, Ferrari L (2018) The occurrence of 275 rare diseases and 47 rare disease groups in Italy. Results from the National Registry of Rare Diseases. Int J Environ Res Public Health 15:1470CrossRefPubMedCentral
14.
Kryger MH, Walid R, Manfreda J (2002) Diagnoses received by narcolepsy patients in the year prior to diagnosis by a sleep specialist. Sleep 25:36e41CrossRef
15.
Morrish E, King MA, Smith IE, Shneerson JM (2004) Factors associated with a delay in the diagnosis of narcolepsy. Sleep Med 5:37–41CrossRefPubMed
16.
Thorpy MJ, Krieger AC (2014) Delayed diagnosis of narcolepsy: characterization and impact. Sleep 15:502–507CrossRef
17.
Taddei RN, Werth E, Poryazova R, Baumann CR, Valko PO (2016) Diagnostic delay innarcolepsy type 1: combining the patients’ and the doctors’ perspectives. J Sleep Res 25:709–715CrossRefPubMed
18.
Thorpy MJ, Hiller G (2017) The medical and economic burden of narcolepsy: implications for managed care. Am Health Drug Benefits 10:233–241PubMedPubMedCentral
19.
Macleod S, Ferrie C, Zuberi SM (2005) Symptoms of narcolepsy in children misinterpreted as epilepsy. Epileptic Disord 7:13–17PubMed
20.
Kauta SR, Marcus CL (2012) Cases of pediatric narcolepsy after misdiagnoses. Pediatr Neurol 47:362–365CrossRefPubMed
21.
Rosenberg R, Kim AY (2014) The AWAKEN survey: knowledge of narcolepsy among physicians and the general population. Postgrad Med 26:78–86CrossRef
22.
Carter LP, Acebo C, Kim A (2014) Patients’ journeys to a narcolepsy diagnosis: a physician survey and retrospective chart review. Postgrad Med 126:216–224CrossRefPubMed
23.
Plazzi G, Pizza F, Palaia V, Franceschini C, Poli F, Moghadam KK, Cortelli P, Nobili L, Bruni O, Dauvilliers Y, Lin L, Edwards MJ, Mignot E, Bhatia KP (2011) Complex movement disorders at disease onset in childhood narcolepsy with cataplexy. Brain 134:3477–3489CrossRefPubMedPubMedCentral
24.
Pizza F, Franceschini C, Peltola H, Vandi S, Finotti E, Ingravallo F, Nobili L, Bruni O, Lin L, Edwards MJ, Partinen M, Dauvilliers Y, Mignot E, Bhatia KP, Plazzi G (2013) Clinical and polysomnographic course of childhood narcolepsy with cataplexy. Brain 136:3787–3795CrossRefPubMedPubMedCentral
25.
Aran A, Einen M, Lin L, Plazzi G, Nishino S, Mignot E (2010) Clinical and therapeutic aspects of childhood narcolepsy-cataplexy: a retrospective study of 51 children. Sleep 33:1457–1464CrossRefPubMedPubMedCentral
26.
Maski K, Steinhart E, Williams D, Scammell T, Flygare J, McCleary K, Gow M (2017) Listening to the patient voice in narcolepsy: diagnostic delay, disease burden, and treatment efficacy. J Clin Sleep Med 13:419–425CrossRefPubMedPubMedCentral
27.
28.
Serra L, Montagna P, Mignot E, Lugaresi E, Plazzi G (2008) Cataplexy features in childhood narcolepsy. Mov Disord 23:858–865CrossRefPubMed
29.
Ingravallo F, Gnucci V, Pizza F, Vignatelli L, Govi A, Dormi A, Pelotti S, Cicognani A, Dauvilliers Y, Plazzi G (2012) The burden of narcolepsy with cataplexy: how disease history and clinical features influence socio-economic outcomes. Sleep Med 13:1293–1300CrossRefPubMed
30.
Dodel R, Peter H, Walbert T et al (2004) The socioeconomic impact of narcolepsy. Sleep 27:1123e8CrossRef
31.
Smolensky MH, Di Milia L, Ohayon MM, et al (2011) Sleep disorders, medical conditions, and road accident risk. Accid Anal Prev; 43:533e48
32.
Jennum P, Ibsen R, Petersen ER et al (2012) Health, social, and economic consequences of narcolepsy: a controlled national study evaluating the societal effect on patients and their partners. Sleep Med 13:1086e93CrossRef
33.
Ohayon MM (2013) Narcolepsy is complicated by high medical and psychiatric comorbidities: a comparison with the general population. Sleep Med 14:488e92CrossRef
34.
Ohayon MM, Black J, Lai C et al (2014) Increased mortality in narcolepsy. Sleep 37:439e44CrossRef
35.
36.
37.
Scammell TE. Clinical features and diagnosis of narcolepsy in adults. Benca R, Eichler AF, eds. UpToDate. Waltham, MA: UpToDate Inc. http://​www.​uptodate.​com. Last access May 28, 2018
38.
Flottorp SA, Oxman AD, Krause J et al (2013) A checklist for identifying determinants of practice: a systematic review and synthesis of frameworks and taxonomies of factors that prevent or enable improvements in healthcare professional practice. Implement Sci 23:8–35
39.
40.
Babiker MO, Prasad M (2015) Narcolepsy in children: a diagnostic and management approach. Pediatr Neurol 52:557–565CrossRefPubMed
41.
Partinen M, Saarenpää-Heikkilä O, IlveskoskIi et al (2012) Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. Plos One 2:e33723CrossRef
42.
Lee J, Na G, Joo EY, Lee M, Lee J (2017) Clinical and polysomnographic characteristics of excessive daytime sleepiness in children. Sleep Breath 21:967–974CrossRefPubMed
43.
Prasad M, Setty G, Ponnusamy A et al (2014) Cataplectic facies: clinical marker in the diagnosis of childhood narcolepsy-report of two cases. Pediatr Neurol 515:517
44.
Dhondt K, Verhelst H, Pevernagie D, Slap F, Van Coster R (2009) Childhood narcolepsy with partial facial cataplexy: a diagnostic dilemma. Sleep Med 10:797–798CrossRefPubMed
45.
Jardri R, Bartels-Velthuis DM et al (2014) From phenomenology to neurophysiological understanding of hallucinations in children and adolescents. Schizophr Bull 40:S221–S232CrossRefPubMedPubMedCentral
46.
Nevsimalova S, Prihodova I, Kemlink D, Lin L, Mignot E (2007) REM behavior disorder (RBD) can be one of the first symptoms of childhood narcolepsy. Sleep Med 8:784–786CrossRefPubMed
47.
Lloyd R, Tippmann-Peikert M, Slocumb N, Kotagal S (2012) Characteristics of REM sleep behavior disorder in childhood. J Clin Sleep Med 8:127PubMedPubMedCentral
48.
Pisko J, Pastorek L, Buskova J, Sonka K, Nevsimalova S (2014) Nightmares in narcolepsy: underinvestigated symptoms? Sleep Med 15:967–972CrossRefPubMed
49.
Antelmi E, Pizza F, Vandi S, Neccia G, Ferri R, Bruni O, Filardi M, Cantalupo G, Liguori R, Plazzi G (2017) The spectrum of REM sleep-related episodes in children with type 1 narcolepsy. Brain 140:1669–1679CrossRefPubMed
50.
Wang Z, Wu H, Stone WS, Zhuang J, Qiu L, Xu X, Wang Y, Zhao Z, Han F, Zhao Z (2016) Body weight and basal metabolic rate in childhood narcolepsy: a longitudinal study. Sleep Med 25:139–144CrossRefPubMed
51.
Ponziani V, Gennari M, Pizza F, Balsamo A, Bernardi F, Plazzi G (2016) Growing up with type 1 narcolepsy: its anthropometric and endocrine features. J Clin Sleep Med 12:1649–1657CrossRefPubMedPubMedCentral
52.
Poli F, Pizza F, Mignot E, Ferri R, Pagotto U, Taheri S, Finotti E, Bernardi F, Pirazzoli P, Cicognani A, Balsamo A, Nobili L, Bruni O, Plazzi G (2013) High prevalence of precocious puberty and obesity in childhood narcolepsy with cataplexy. Sleep 36:175–181CrossRefPubMedPubMedCentral
53.
Dahmen N, Bierbrauer J, Kasten M (2001) Increased prevalence of obesity in narcoleptic patients and relatives. Eur Arch Psychiatry Clin Neurosci 251:85–89CrossRefPubMed
54.
Vetrugno R, D’Angelo R, Moghadam KK et al (2010) Behavioural and neurophysiological correlates of human cataplexy: a video-polygraphic study. Clin Neurophysiol 121:153–162CrossRefPubMed
55.
Overeem S, van Nues SJ, van der Zande WL, Donjacour CE, van Mierlo P, Lammers GJ (2011) The clinical features of cataplexy: a questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency. Sleep Med 12(12):12–18CrossRefPubMed
56.
Pizza F, Antelmi E, Vandi S, Meletti S, Erro R, Baumann CR, Bhatia KP, Dauvilliers Y, Edwards MJ, Iranzo A, Overeem S, Tinazzi M, Liguori R, Plazzi G (2018) The distinguishing motor features of cataplexy: a study from video-recorded attacks. Sleep 41(5). https://​doi.​org/​10.​1093/​sleep/​zsy026
57.
Plazzi G, Serra L, Ferri R (2008) Nocturnal aspects of narcolepsy with cataplexy. Sleep Med Rev 12:109–128CrossRefPubMed
58.
Dauvilliers Y, Jennum P, Plazzi G (2013) Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy. Sleep Med 14:775–781CrossRefPubMed
59.
Franceschini C, Ferri R, Pizza F, Ricotta L, Vandi S, Detto S, Poli F, Pruneti C, Mazzetti M, Cipolli C, Lugaresi E, Plazzi G (2011) Motor events during REM sleep in patients with narcolepsy-cataplexy: a video-polysomnographic pilot study. Sleep Med 12:S59–S63CrossRefPubMed
60.
Cipolli C, Franceschini C, Mattarozzi K, Mazzetti M, Plazzi G (2011) Overnight distribution and motor characteristics of REM sleep behaviour disorder episodes in patients with narcolepsy-cataplexy. Sleep Med 12:635–640CrossRefPubMed
61.
Rinaldi R, Vignatelli L, D’Alessandro R et al (2001) Validation of symptoms related to excessive daytime sleepiness. Neuroepidemiology 20:248–256CrossRefPubMed
62.
Vignatelli L, Plazzi G, Barbato A, Ferini-Strambi L, Manni R, Pompei F, D’Alessandro R, GINSEN (Gruppo Italiano Narcolessia Studio Epidemiologico Nazionale (2003) Italian version of the Epworth sleepiness scale: external validity. Neurol Sci 23:295–300CrossRefPubMed
63.
Bruni O, Violani C, Luchetti A, Miano S, Verrillo E, Di Brina C, Valente D (2004) The sleep knowledge of pediatricians and child neuropsychiatrists. Sleep and Hypnosis 6:130–138
Metadata
Title
Red Flags for early referral of people with symptoms suggestive of narcolepsy: a report from a national multidisciplinary panel
Authors
L. Vignatelli
E. Antelmi
I. Ceretelli
M. Bellini
C. Carta
P. Cortelli
L. Ferini-Strambi
R. Ferri
R. Guerrini
F. Ingravallo
V. Marchiani
F. Mari
G. Pieroni
F. Pizza
M. C. Verga
E. Verrillo
D. Taruscio
Giuseppe Plazzi
Publication date
01-03-2019
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 3/2019
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-018-3666-x

Other articles of this Issue 3/2019

Neurological Sciences 3/2019 Go to the issue

Original Article

Lack of association between valproic acid response and polymorphisms of its metabolism, transport, and receptor genes in children with focal seizures

Original Article

Clinical and genetic characterization of an Italian family with slow-channel syndrome

Original Article

Completeness of circle of Willis and white matter hyperintensities in patients with severe internal carotid artery stenosis

Letter to the Editor

Stroke or Stramonium? A novel stroke mimic

Original Article

Cortical degeneration in chronic traumatic encephalopathy and Alzheimer’s disease neuropathologic change

Original Article

Incidence study of Guillain-Barré syndrome in the province of Ferrara, Northern Italy, between 2003 and 2017. A 40-year follow-up