“Weak with Laughter”—Cataplexy as a Hint for Early Diagnosis of Niemann–Pick Type C?

Cataplexy is described as a paroxysmal transient loss of muscle tone with retained consciousness provoked by strong emotions like laughter and fear.[1]

The pathophysiology of cataplexy, especially in the context of Niemann–Pick type C (NPC), is not fully understood. However the association of lower orexin levels in cerebrospinal fluid (CSF) in patients with cataplexy suggests that these episodes can be a result of loss of orexin neurons.[2] Usually cataplexy occurs in narcoleptic patients and is also reported in Angelman's syndrome[1] and animals, for example, in dogs.[3]

Our patient is an 8-year-old boy who was diagnosed with a mutation of NPC1 at age 6. At 3 years, he started showing developmental regression, especially of speech. Then he had attacks of bilateral loss of muscle tone starting in head and neck region often spreading distally with subsequent falling. These attacks are provoked by laughter and can sometimes be anticipated ([Video 1]; available in the online version). They occurred before the typical vertical gaze palsy started. We think that cataplectic episodes can be a hint for early diagnosis of the disease.[4] This is relevant, as there is a treatment option which can have a favorable impact on the course of NPC.[5] In our patient, however, it could not prevent the severe course.

Video 1 Eight-year-old boy with Niemann-Pick Type C showing bilateral loss of muscle tone being provoked by laughter. In the second part of the video, he starts falling down subsequently but is stabilised by a physical therapist.

Publication History

Received: 26 May 2021

Accepted: 01 July 2021

Article published online:
01 December 2021

• References

• 1 Lima FCB, do Nascimento Junior EB, Teixeira SS, Coelho FM, Oliveira GDP. Thinking outside the box: cataplexy without narcolepsy. Sleep Med 2019; 61: 118-121
• 2 Imanishi A, Kawazoe T, Hamada Y. et al. Early detection of Niemann-Pick disease type C with cataplexy and orexin levels: continuous observation with and without Miglustat. Orphanet J Rare Dis 2020; 15 (01) 269
• 3 Tonokura M, Fujita K, Nishino S. Review of pathophysiology and clinical management of narcolepsy in dogs. Vet Rec 2007; 161 (11) 375-380
• 4 Pedroso JL, Fusão EF, Ladeia-Frota C. et al. Teaching video neuroimages: gelastic cataplexy as the first neurologic manifestation of Niemann-Pick disease type C. Neurology 2012; 79 (22) e189-e189
• 5 Lyseng-Williamson KA. Miglustat: a review of its use in Niemann-Pick disease type C. Drugs 2014; 74 (01) 61-74