Cataplexy and Sleep Disorders in Niemann-Pick Type C Disease
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Niemann-Pick disease type C (NP-C) is a rare and progressive autosomal recessive disease leading to disabling neurological manifestation and premature death. The disease is prone to underdiagnosis because of its highly heterogeneous presentation. NP-C is characterized by visceral, neurological, and psychiatric manifestation, and its clinical picture varies according to age at onset. Although cataplexy is one of its characteristic symptoms, particularly in the late infantile and juvenile form, sleep disturbances are described only exceptionally. A combination of splenomegaly, vertical supranuclear gaze palsy, and cataplexy creates a most useful suspicion index tool for the disease. In adolescent and adult patients, when intellectual deterioration progresses and emotional reactions become flat, cataplexy usually disappears. Pathological findings in the brainstem in NP-C mouse model are compatible with the patients’ symptoms including cataplexy. The authors observed cataplexy in 5 (3 with late infantile and 2 with juvenile form) out of 22 NP-C cases followed up in the past 20 years.
KeywordsNiemann-Pick type C Clinical symptoms Cataplexy Sleep disturbance Hypocretin Personal observation
Supported by PRVOUK-P26/LF1/4, IGA MZ CR NT 13238-4/2012, and RVO-VFN 64165/2014.
Compliance with Ethics Guidelines
Conflict of Interest
Sona Nevsimalova is supported by PRVOUK-P26/LF1/4, IGA MZ CR NT 13238-4/2012, and RVO-VFN 64165/2014.
Vera Malinova has received travel support from Actelion (NPC and Gaucher meetings), and paid travel accommodations for LSD congresses and is supported by RVO-VFN 64165/2014.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
A video shows cataplectic attack in a 13-year-old boy with juvenile form of Niemann-Pick type C disease during the electroencephalographic monitoring. The long attack is evoked by laugh (“gelastic cataplexy”). We are thankful to Jan Hadac, MD, PhD (Department of Pediatric Neurology, Thomayer’s Hospital, Prague, Czech Republic) for a possibility to show this video. (WMV 2247 kb)
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- 3.••Patterson MC, Hendriksz CJ, Walterfang M, Sedel F, Vanier MT, Wijburg F. Recommendations for the diagnosis and management of Niemann-Pick disease type C: an update. Mol Genet Metab. 2012;106:330–44. The authors report points of consensus among experts in the diagnosis and treatment of NP-C. The article serves as an update to the original guidelines providing further information on detection, diagnostic methods, monitoring disease progression, and therapy.PubMedCrossRefGoogle Scholar
- 6.•Sevin M, Lesca G, Baumann N, Millat G, Lyon-Caen O, Vanier MT, et al. The adult form of Niemann-Pick disease type C. Brain. 2007;130:120–33. The most extensive study of adults with NP-C improving the knowledge of cognitive/psychiatric stages of the disease before the occurrence of classical neurological lesions.PubMedCrossRefGoogle Scholar
- 8.Nevsimalova S. Genetic disorders and sleepiness. In: Thorpy MJ, Billiard M, editors. Sleepiness—causes, consequences and symptoms. New York: Cambridge University Press; 2011. p. 335–50.Google Scholar
- 9.••Mengel E, Klunemann HH, Lourenco CM, Hendriksz CJ, Sedel F, Walterfang M, et al. Niemann-Pick disease type C symptomatology: an expert-based clinical description. Orphanet J Rare Dis. 2013;8:166. A review summarizes NP-C signs and symptoms and, particularly, their combinations. NP-C Suspicion Index Tool is highly predictive for the diagnosis.PubMedCentralPubMedCrossRefGoogle Scholar
- 13.••Wraith JE, Imrie J. New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat. Ther Clin Risk Manag. 2009;5:877–87. Findings demonstrate clinically relevant beneficial effects of miglustat on neurological disease progression in adult, juvenile, and pediatric patients with NP-C, particularly those diagnosed in late childhood (6–11 years) and juveniles and adults (12 years and older,) compared with those diagnosed in early childhood (younger than 6 years).PubMedCentralPubMedCrossRefGoogle Scholar
- 16.••Salsano E, Umeh C, Rufa A, Pareyson D, Zee DS. Vertical supranuclear gaze palsy in Niemann-Pick type C disease. Neurol Sci. 2012;33:1225–32. Vertical supranuclear gaze palsy (VSGP)—as a typical clinical feature in patients with Niemann-Pick type C disease—is present in approximately 65 % of the cases. Together with gelastic cataplexy is an important risk indicator of the disease.PubMedCrossRefGoogle Scholar
- 17.••Wraith JE, Baumgartner MR, Bembi B, Covanis A, Levade T, Mengel E, et al. Recommendation on the diagnosis and management of Niemann-Pick disease type C. Mol Genet Metab. 2009;98:152–65. Expert panel presents key aspects of the clinical management of the disease in children, juveniles and adults, and provides recommendations based on consensus between those experts. PubMedCrossRefGoogle Scholar
- 21.American Academy of Sleep Medicine. International Classification of Sleep Disorders, 2nd ed, Diagnostic and coding manual. Westchester: American Academy of Sleep Medicine; 2005.Google Scholar
- 22.••American Academy of Sleep Medicine. International Classification of Sleep Disorders, 3rd ed. Darien, Illinois: American Academy of Sleep Medicine 2014. The new classification distinguishes between two basic forms of narcolepsy—narcolepsy type 1 (with hypocretin-1 deficiency) and narcolepsy type 2 (without hypocretin-1 deficiency). Google Scholar
- 26.••Nishino S, Kanbayashi T. Symptomatic narcolepsy, cataplexy and hypersomnia, and their implication in the hypothalamic hypocretin/orexin system. Sleep Med Rev. 2005;9:269–310. A survey of secondary (symptomatic) cases of narcolepsy as well as isolated cataplexy in children and adults reviewed in the literature.PubMedCrossRefGoogle Scholar
- 29.Pedroso JL, Fusao EF, Ladeia-Frota C, Arita JH, Barsottini OG, Masruha MR, Pereira LC. Teaching video neuroimages: gelastic cataplexy as the firs neurologic manifestation of Niemann-Pick disease type C. In: MSV Elkind (ed). Resident and fellow section, American Academy of Neurology 2012, e189.Google Scholar
- 32.••Vankova J, Stepanova I, Jech R, Elleder M, Lin L, Mignot E, et al. Sleep disturbance and hypocretin deficiency in Niemann-Pick disease type C. Sleep. 2003;26:427–30. One of the first articles presents hypocretin deficiency in NP-C patients. All patients underwent nocturnal polysomnography and multiple sleep latency test (MSLT). Changes of sleep architecture (including sleep microstructure) were found, and majority of the patients demonstrated shortened mean sleep latency in MSLT.PubMedGoogle Scholar
- 39.••Luan Z, Saito Y, Miyata H, Ohama E, Ninomiya H, Ohno K. Brainstem neuropathology. J Neurol Sci. 2008;268:108–16. The neuropathological changes observed in the brainstem of NPC1−/− mice are largely compatible with the clinical symptoms (including cataplexy) and reported neuropathology in Niemann-Pick type C patients.PubMedCrossRefGoogle Scholar