Although the circuitry is unclear, this supports that orexin system is indeed involved in narcolepsy-cataplexy in NPC patients. However with Miglustat treatment, the orexin levels stabilized or improved, along with other general symptoms. Low or intermediate orexin levels could further decrease due to reduction in the neuronal function in the orexin system, accelerating the patients’ NPC pathophysiology. Our study indicates that orexin level measurements can be an early alert of potential NPC. The CSF orexin levels of NPC patients were significantly higher than those of patients with narcolepsy-cataplexy and lower than those of patients with idiopathic hypersomnia, which was considered as the control group with normal CSF orexin levels. For cases without Miglustat treatment, their conditions worsened generally.

In 5 cases with Miglustat treatment, their symptoms stabilized or improved.

In 4 cases without cataplexy, their orexin levels were normal. Six NPC patients with cataplexy had low or intermediate orexin levels. We compared CSF orexin levels among NPC, narcoleptic and idiopathic hypersomnia patients. NPC diagnosis was biochemically confirmed in all 10 patients, from which 8 patients with NPC1 gene were identified. Ten patients with NPC were included in the study (5 males and 5 females). In this current study, we examined CSF orexin levels in the 10 patients of NPC with and without cataplexy, which supports previous findings. Some cases frequently display narcolepsy-like symptoms, including cataplexy which was reported in 26% of all NPC patients and was more often recorded among late-infantile onset (50%) and juvenile onset (38%) patients. Symptoms include hepatosplenomegaly, vertical supranuclear saccadic palsy, ataxia, dystonia, and dementia. The current therapeutic target is oriented towards hypocretine agonists, histamine (an arousal system) H3 antagonists and immunosuppressants.Niemann-Pick type C (NPC) is an autosomal recessive and congenital neurological disorder characterized by the accumulation of cholesterol and glycosphingolipids. The treatment of narcolepsy includes stimulants against sleepiness (modafinil, methylphenidate), anticataplectic drugs (antidepressants) and sodium oxybate. The cause of human narcolepsy remains unknown, however an autoimmune process is most probable.

The deficiency of the hypocretin system is well-established in animal models of narcolepsy (murine and canine narcolepsy) but also in human narcoleptics with a 90% reduction of CSF hypocretin levels in relation with an early loss of hypocretin neurons. In contrast, a low hypocretin levels (values below 110 pg/ml) in the cerebrospinal fluid (CSF) was highly specific for narcolepsy with cataplexy. HLA typing shows an association with HLA DQB1*0602 in more than 92% of cases but was not included in the new diagnostic criteria. Narcolepsy with cataplexy remains a clinical diagnosis but nighttime and daytime polysomnography (multiple sleep latency tests) are useful to document a mean sleep latency below 8 min and at least two sleep-onset REM periods. Other less consistent symptoms include hypnagogic hallucinations, sleep paralysis, sleep maintenance insomnia, REM sleep behavior disorders, attention deficit and weight gain at disease onset. The main features are excessive daytime sleepiness and cataplexy or sudden loss of muscle tone triggered by emotional situations. Its onset, from childhood to the fifties, peaks in the second decade. Narcolepsy is a rare, disabling sleep disorder, with a prevalence of 20 to 30 per 100,000.

Narcolepsy cataplexy csf deficiency