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Narcolepsy with Cataplexy Mimicry: The Strange Case of Two Sisters

2013; American Academy of Sleep Medicine; Volume: 09; Issue: 06 Linguagem: Inglês

10.5664/jcsm.2764

1550-9397

Fabio Pizza, Stefano Vandi, Francesca Poli, Keivan Kaveh Moghadam, Christian Franceschini, Claudia Crilly Bellucci, Carlo Cipolli, Francesca Ingravallo, G Natalini, Emmanuel Mignot, Giuseppe Plazzi,

Memory and Neural Mechanisms

Free AccessEMGNarcolepsy with Cataplexy Mimicry: The Strange Case of Two Sisters Fabio Pizza, M.D., Ph.D., Stefano Vandi, RPSGT, Francesca Poli, M.D., Ph.D., Keivan Kaveh Moghadam, M.D., Christian Franceschini, Psy.D., Ph.D., Claudia Bellucci, Psy.D., Carlo Cipolli, Psy.D., Francesca Ingravallo, M.D., Ph.D., Giuliana Natalini, M.D., Emmanuel Mignot, M.D., Ph.D., F.A.A.S.M., Giuseppe Plazzi, M.D., Ph.D. Fabio Pizza, M.D., Ph.D. Department of Biomedical and Neuromotor Sciences, University of Bologna, and IRCCS Istituto delle Scienze Neurologiche, AUSL di Bologna, Bologna, Italy , Stefano Vandi, RPSGT Department of Biomedical and Neuromotor Sciences, University of Bologna, and IRCCS Istituto delle Scienze Neurologiche, AUSL di Bologna, Bologna, Italy , Francesca Poli, M.D., Ph.D. Department of Biomedical and Neuromotor Sciences, University of Bologna, and IRCCS Istituto delle Scienze Neurologiche, AUSL di Bologna, Bologna, Italy , Keivan Kaveh Moghadam, M.D. Department of Biomedical and Neuromotor Sciences, University of Bologna, and IRCCS Istituto delle Scienze Neurologiche, AUSL di Bologna, Bologna, Italy , Christian Franceschini, Psy.D., Ph.D. Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy , Claudia Bellucci, Psy.D. Department of Psychology, University of Bologna, Bologna, Italy , Carlo Cipolli, Psy.D. Department of Psychology, University of Bologna, Bologna, Italy , Francesca Ingravallo, M.D., Ph.D. Department of Medicine and Public Health, Section of Legal Medicine, University of Bologna, Bologna, Italy , Giuliana Natalini, M.D. Area Vasta 2, Ancona, Italy , Emmanuel Mignot, M.D., Ph.D., F.A.A.S.M. Center for Narcolepsy, Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA , Giuseppe Plazzi, M.D., Ph.D. Address correspondence to: Giuseppe Plazzi, Dipartimento di Scienze Biomediche e Neuromotorie, Via Ugo Foscolo 7, 40123, Bologna, Italy051/4966926051/4966098 E-mail Address: [email protected] Department of Biomedical and Neuromotor Sciences, University of Bologna, and IRCCS Istituto delle Scienze Neurologiche, AUSL di Bologna, Bologna, Italy Published Online:June 15, 2013https://doi.org/10.5664/jcsm.2764Cited by:11SectionsAbstractPDFSupplemental Material ShareShare onFacebookTwitterLinkedInRedditEmail ToolsAdd to favoritesDownload CitationsTrack Citations AboutABSTRACTWe report on two sisters, 17 and 12 years of age, with clinical features suggesting narcolepsy with cataplexy (NC): daytime sleepiness, spontaneous and emotionally triggered sudden falls to the ground, and overweight/obesity. MSLT showed borderline sleep latency, with 1 and 0 sleep onset REM periods. HLA typing disclosed the DQB1*0602 allele. Video-polygraphy of the spells ruled out NC diagnosis by demonstrating their easy elicitation by suggestion, with wake EEG, electromyo-graphic persistence of muscle tone, and stable presence of tendon reflexes (i.e., pseudo-cataplexy), together with normal cerebrospinal hypocretin-1 levels.Our cases emphasize the need of a clear depiction of cataplexy pattern at the different ages, the usefulness of examining ictal neurophysiology, and collecting all available disease markers in ambiguous cases.Citation:Pizza F; Vandi S; Poli F; Moghadam KK; Fran-ceschini C; Bellucci C; Cipolli C; Ingravallo F; Natalini G; Mignot E; Plazzi G. Narcolepsy with cataplexy mimicry: the strange case of two sisters. J Clin Sleep Med 2013;9(6):611-612.INTRODUCTIONNarcolepsy with cataplexy (NC) is a rare hypersomnia of central origin characterized by daytime sleepiness, cataplexy (sudden losses of muscle tone triggered by emotions, pathognomonic symptom), and other REM sleep disturbances. Reduced levels of cerebrospinal hypocretin-1 (hcrt-1 < 110 pg/mL) or ≥ 2 sleep onset REM periods (SOREMP) at MSLT should, "whenever possible" confirm NC diagnosis according to the International Classification of Sleep Disorders (ICSD-2).1 We report two ambiguous cases who were sent to our center with suspected NC, claiming the need to document accurately cataplexy features within NC assessment.REPORT OF CASESPatient 1Patient 1 is a 17-year-old female presenting with frequent episodes (up to 5-6 per day) of sudden shortness of breath since age 13 years, followed by occasional apparent loss of consciousness. Since 14 years of age, she has had sudden falls to the ground, occurring both while standing or sitting and elicited by emotions, with immobility for up to few minutes. After an initial cluster, episodes frequency settled to 1-2 per month. She also increased weight and, at 16 years, daytime sleepiness appeared. At our observation she had a BMI of 31.24 kg/m2 and an Epworth Sleepiness Scale (ESS) score of 12. Cardiological evaluation and testing and brain MRI were normal. During 48-h polysomnography (PSG) she had SOREMPs in both daytime and nighttime sleep in the absence of sleep disordered breathing (apnea-hypopnea index [AHI] of 0/h). MSLT showed borderline sleep latency (9 min) with 1/5 SOREMP. Human Leucocyte Antigen typing revealed the HLA-DQB1*0602 allele. A typical spell, evoked by a suggestion maneuver, was recorded during video-PSG, showing ictal persistence of EMG muscle tone, deep tendon reflexes, and normal wake EEG (Video 1). Hcrt-1 level was in the normal range (364.4 pg/mL). A diagnosis of NC was excluded. Since we communicated the noncataplectic nature of the spells, their frequency has decreased to 2-3 episodes per year.Video polygraphy of pseudo-cataplexyVideo 1 shows an instance where Patient 1 was standing while a placebo suggestion was performed. She abruptly fell on the ground—EMG showed initially increased then persistent muscle tone, and EEG, partially masked by artifacts, showed wake activity. While Patient 1 was recumbent and apparently unconscious, brisk reflexes could be easily evoked, confirming the non-cataplectic nature of the spell. The episode ended after another suggestion maneuver and while the doctor was reassuring Patient 1 that the episode would soon vanish. Polygraphic montage included EEG (C3-A2; O1-A2; Cz-A2), EOG (ROC-A1; LOC-A1), EMG (chin, right masseter, nuchal, right sternocleidomastoid, right and left deltoid, right and left carpus extensor, right and left anterior tibial muscles), ECG, and thoraco-abdominal belt from the top to the bottom.Patient 2Patient 2, the 12-year-old sister of Patient 1, had sudden episodes of vertigo followed by apparent brief loss of consciousness and falls to the ground with unresponsiveness to external stimuli for a few seconds to some minutes since 11 years of age. These episodes, after an initial cluster of 10 per day over a week, decreased to 1-2 per day. According to parent's report, the episodes were similar to those of Patient 1. Psychiatric evaluation disclosed attention deficit hyperactivity disorder (ADHD), and normal head-up tilt table test excluded vasovagal syncope. At our evaluation, she complained mild restless legs symptoms and daytime sleepiness (ESS score of 15); sleep talking since childhood was reported. Her BMI was 29.7 kg/m2. MSLT showed borderline sleep latency (9 min 12 sec). No SOREMP occurred during daytime or nighttime sleep on 48-h PSG (AHI = 0/h). She was HLA-DQB1*0602 positive and had normal brain MRI. Video-PSG of a spell occurring while watching funny videos showed persistence of wake EEG activity, EMG muscle tone, and deep tendon reflexes (Video 2). Hcrt-1 was in the normal range (253.7 pg/mL). Atomoxetine was given for ADHD, and she reported improved daytime sleepiness and significant spells reduction (1-2 per month).Video polygraphy of pseudo-cataplexyVideo 2 shows an instance where Patient 2 was standing and watching funny videos and abruptly fell on the ground— EMG initially showed a reinforcement then a persistence of muscle tone and EEG, masked by artifacts, wake activity. While Patient 2 was recumbent and unresponsive to external stimuli, osteo-tendinous reflexes could be easily evoked, also when muscle tone was apparently of low amplitude on EMG channels. Polygraphic montage included EEG (C3-A2; O1-A2; Cz-A2), EOG (ROC-A1; LOC-A1), EMG (chin, right masseter, nuchal, right sternocleidomastoid, right and left deltoid, right and left carpus extensor, right and left anterior tibial muscles), ECG, and thoraco-abdominal belt from the top to the bottom.DISCUSSIONOur cases show that the diagnosis of cataplexy based on clinical history alone may be misleading and suggest the need to further frame cataplexy and its mimics by documenting the episodes in the diagnostic work-up of suspected NC. According to ICSD-2, MSLT should be performed in the absence of a definite history of cataplexy, and HLA typing is neither sensitive nor specific for NC diagnosis confirmation.1 Indeed, as cataplexy is easy to document and peculiar, especially in children close to disease onset,2 we suggest the need to search for it considering ictal video-PSG useful in uncertain cases,3 and also for phenotype-genotype research purposes. NC objective biomarkers, namely SOREMPs and low/undetectable hcrt-1, have to be investigated in all challenging patients, and normal hcrt-1 may occur only in peculiar cases.4 Differential diagnosis of cataplexy should include a careful work-up to rule out cardiovascular conditions such as vasovagal syncope,5 drop attacks,6 and epilepsy.7 Misdiagnosing as NC other neurologic or psychiatric disorders, or cases of malingering, may have serious consequences for patients and their families, as well as high costs for the society. Overlaps between NC and psychiatric traits3 or disorders8 may also exist and require multidisciplinary approach and further investigations.9DISCLOSURE STATEMENTThis was not an industry supported study. Dr. Plazzi has consulted for UCB Pharma and JAZZ Pharmaceuticals. Dr. Mignot receives research support from GlaxoSmith-Kline, Jazz Pharmaceuticals, and Novo Nordisk. The other authors have indicated no financial conflicts of interest.REFERENCES1 American Academy of Sleep MedicineInternational classification of sleep disorders: diagnostic and coding manual2nd edWestchester, IL: American Academy of Sleep Medicine; 2005. Google Scholar2 Plazzi G, Pizza F, Palaia Vet al.Complex movement disorders at disease onset in childhood narcolepsy with cataplexy. Brain; 2011;134:3480-92, 21930661. CrossrefGoogle Scholar3 Plazzi G, Khatami R, Serra L, Pizza F, Bassetti CLPseudocataplexy in narcolepsy with cataplexy. Sleep Med; 2010;11:591-4, 20471315. CrossrefGoogle Scholar4 Khatami R, Maret S, Werth Eet al.Monozygotic twins concordant for narcolepsy-cataplexy without any detectable abnormality in the hypocretin (orexin) pathway. Lancet; 2004;363:1199-200, 15081654. CrossrefGoogle Scholar5 Totah AR, Benbadis SRGelastic syncope mistaken for cataplexy. Sleep Med; 2002;3:77-8, 14592259. CrossrefGoogle Scholar6 Plazzi G, Tonon C, Rubboli Get al.Narcolepsy with cataplexy associated with holoprosencephaly misdiagnosed as epileptic drop attacks. Mov Disord; 2010;25:788-90, 20131387. CrossrefGoogle Scholar7 Plazzi G, Tinuper PPraxis-induced seizures misdiagnosed as cataplexy: a case report. Mov Disord; 2008;23:2105-7, 18709676. Google Scholar8 Miano S, Parisi P, Villa MPThe sleep phenotypes of attention deficit hyperactivity disorder: the role of arousal during sleep and implications for treatment. Med Hypotheses; 2012;79:147-53, 22608760. CrossrefGoogle Scholar9 Fortuyn HA, Mulders PC, Renier WO, Buitelaar JK, Overeem SNarcolepsy and psychiatry: an evolving association of increasing interest. Sleep Med; 2011;12:714-9, 21689985. CrossrefGoogle Scholar Previous article Next article FiguresReferencesRelatedDetailsCited by A standardized test to document cataplexyVandi S, Pizza F, Antelmi E, Neccia G, Iloti M, Mazzoni A, Avoni P and Plazzi G Sleep Medicine, 10.1016/j.sleep.2017.08.021, Vol. 53, , (197-204), Online publication date: 1-Jan-2019. The MSLT is Repeatable in Narcolepsy Type 1 But Not Narcolepsy Type 2: A Retrospective Patient StudyRuoff C, Pizza F, Trotti L, Sonka K, Vandi S, Cheung J, Pinto S, Einen M, Simakajornboon N, Han F, Peppard P, Nevsimalova S, Plazzi G, Rye D and Mignot E Journal of Clinical Sleep Medicine, Vol. 14, No. 01, (65-74), Online publication date: 15-Jan-2018. The clinical spectrum of childhood narcolepsyPostiglione E, Antelmi E, Pizza F, Lecendreux M, Dauvilliers Y and Plazzi G Sleep Medicine Reviews, 10.1016/j.smrv.2017.04.003, Vol. 38, , (70-85), Online publication date: 1-Apr-2018. Automatic detection of cataplexyBartolini I, Pizza F, Di Luzio A, Neccia G, Antelmi E, Vandi S and Plazzi G Sleep Medicine, 10.1016/j.sleep.2018.07.018, Vol. 52, , (7-13), Online publication date: 1-Dec-2018. The distinguishing motor features of cataplexy: a study from video-recorded attacksPizza F, Antelmi E, Vandi S, Meletti S, Erro R, Baumann C, Bhatia K, Dauvilliers Y, Edwards M, Iranzo A, Overeem S, Tinazzi M, Liguori R and Plazzi G Sleep, 10.1093/sleep/zsy026, Vol. 41, No. 5, Online publication date: 1-May-2018. Cataplexy and Its Mimics: Clinical Recognition and ManagementPillen S, Pizza F, Dhondt K, Scammell T and Overeem S Current Treatment Options in Neurology, 10.1007/s11940-017-0459-0, Vol. 19, No. 6, Online publication date: 1-Jun-2017. HypersomniaSaini P and Rye D Sleep Medicine Clinics, 10.1016/j.jsmc.2016.10.013, Vol. 12, No. 1, (47-60), Online publication date: 1-Mar-2017. Paruthi S and Kotagal S Narcolepsy in Childhood Narcolepsy, 10.1007/978-3-319-23739-8_6, (51-67), . The ICSD-3 and DSM-5 guidelines for diagnosing narcolepsy: clinical relevance and practicalityRuoff C and Rye D Current Medical Research and Opinion, 10.1080/03007995.2016.1208643, Vol. 32, No. 10, (1611-1622), Online publication date: 2-Oct-2016. Nocturnal Sleep Dynamics Identify Narcolepsy Type 1Pizza F, Vandi S, Iloti M, Franceschini C, Liguori R, Mignot E and Plazzi G Sleep, 10.5665/sleep.4908, Vol. 38, No. 8, (1277-1284), Online publication date: 1-Aug-2015. Sleep in Psychogenic Nonepileptic Seizures and Related DisordersPavlova M, Allen R and Dworetzky B Clinical EEG and Neuroscience, 10.1177/1550059414560565, Vol. 46, No. 1, (34-41), Online publication date: 1-Jan-2015. Volume 09 • Issue 06 • June 15, 2013ISSN (print): 1550-9389ISSN (online): 1550-9397Frequency: Monthly Metrics History Submitted for publicationSeptember 1, 2012Submitted in final revised formNovember 1, 2012Accepted for publicationNovember 1, 2012Published onlineJune 15, 2013 Information© 2013 American Academy of Sleep MedicineKeywordsnarcolepsy with cataplexyvideo polysomnographyhypocretin-1Childhoodpseudo cataplexyACKNOWLEDGMENTSWork for this study was performed at Dipartimento di Scienze Biomediche e Neuromotorie (formerly Dipartimento di Scienze Neurologiche), Via Ugo Foscolo 7, 40123, Bologna, Italy.PDF download