The secondary narcolepsycataplexy

Association of cataplexy with EDS with another disorder of the brain was first reported in the early 1900. These associations includes tumors, localized most frequently to the diencephalon or to the brain stem, other diencephalic lesions (e.g. , large arterio-venous malformation, or lesions secondary to ischemic events), multiple sclerosis with plaques in the diencephalon, head injury, encephalitis, etc. In young children, Niemann-Pick disease type C, characterized by hepatosplenomegaly, progressive ataxia, dystonia, dementia and vertical supranuclear opthalmoplegia, is often associated with cataplexy early in life, as pointed out by Challamel et al. [63]. Cat-aplexy was noted much earlier in these children with Niemann-Pick, than in a group of prepubertal children [35] with a mean age of onset of 6years [63-66]. The other cause of very early onset of secondary cataplexy is craniopharyngioma. This tumor is one of the most common brain tumors in children and account for 9 % of all pediatric intracranial tumors (0.5-2 cases/million population per year) [67]. They often present between 5 and 10 years of age. As the tumors grow, they can involve the pituitary, optic chiasm, and the hypothalamus. They may lead to severe obesity, hypoventilation, and abrupt bilateral muscle weakness. Resection of the tumor often involves hypothalamic lesions and cataplexy and other symptoms may persist. If the craniopharyngioma has not invaded the hypothalamus, the surgical trauma related to the tumor removal may be responsible for a transient cataplexy that will recede progressively [68]. However, when cataplexy is present before surgery, removal of the tumor is not associated with regression of cataplexy. With the discovery of the HCRT/orexin system, and the possibility of measuring CSF HCRT-1 in patients with cataplexy, EDS and other symptoms associated with narcolepsy, several case reports or reports of short series of neurological lesions, mostly tumors, have documented that lesions of the lateral and posterior hypothalamus, independently of its mechanism, lead to lesions of HCRT-producing neurons associated with development of EDS and cataplexy [69-72]. Some cases may present a diagnosis challenge. As an example, hypothalamic astrocytoma leads to obesity, pseudo Pradder-Willi syndrome and associated atypical cataplexy. In this secondary cataplexy, the abrupt muscle weakness may not be triggered by laughter [72], and, depending on the onset of the neurological syndrome, may be seen very early in life (such as in Niemann-Pick type C) [63-66] or late in life. In one reprot, an association was demonstrated between the development of cataplexy with very little sleepiness and clinical symptoms of limbic encephalitis [73], in which an anti-Ma 2 antibody test was positive, and a further search revealed a testicular cancer. Neurological symptoms precede the diagnosis of cancer in 50 % of paraneoplastic syndromes. The presence of cataplexy out of the usual age range, the presence of atypical cataplexy, development of cataplexy without clear association with other symptoms of narcolepsy must raise suspicion, and further neurological and other evaluations are warranted to prevent a rare paraneoplastic syndrome or a primary cancer site being missed. That there can be an immunological involvement in the narcolepsy syndrome and paraneoplastic syndromes is an interesting observation.

Overall, however, secondary cataplexies are associated with specific lesions located in the lateral and posterior hypothalamus, involving the HCRT/orexin neurons.

These lesions can be seen at brain imaging. Occasionally, neurological lesions involve the brain stem, interrupting the descending pathways of the inhibitory reticular formation of Magoun and Rhine, responsible for maintenance of the active inhibition. Isolated cataplexy has been seen with a pontine pilocystic astrocytoma [74], variable EDS with brain stem glioblastoma [75], and subependynoma of fourth ventricle [76]. A 'status cataplecticus' was reported with a midbrain tumor [77].

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