Hypocretin Deficiency Associated with Narcolepsy Type 1 and Central Hypoventilation Syndrome in Neurosarcoidosis of the Hypothalamus.

We report a case of a 53-year-old man presenting with depressed alertness and severe excessive sleepiness in the setting of neurosarcoidosis. Neuroimaging demonstrated hypothalamic destruction due to sarcoidosis with a CSF hypocretin level of 0 pg/mL. The patient also experienced respiratory depression that presumably resulted from hypocretin-mediated hypothalamic dysfunction as a result of extensive diencephalic injury. This is a novel case, demonstrating both hypocretin deficiency syndrome, as well as respiratory dysfunction from destruction of hypocretin neurons and extensive destruction of key diencephalic structures secondary to the underlying neurosarcoidosis.

Hypocretin-1 deficiency in a girl with ROHHAD syndrome.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare and complex pediatric syndrome, essentially caused by dysfunction of 3 vital systems regulating endocrine, respiratory, and autonomic nervous system functioning. The clinical spectrum of ROHHAD is broad, but sleep/wake disorders have received relatively little attention so far, although the central hypothalamic dysfunction would make the occurrence of sleep symptoms likely. In this case report, we expand the phenotype of ROHHAD with a number of striking sleep symptoms that together can be classified as a secondary form of narcolepsy. We present a 7-year-old girl with ROHHAD who displayed the classic features of narcolepsy with cataplexy: excessive daytime sleepiness with daytime naps, visual hallucinations, and partial cataplexy reflected in intermittent loss of facial muscle tone. Nocturnal polysomnography revealed sleep fragmentation and a sleep-onset REM period characteristic for narcolepsy. The diagnosis was confirmed by showing an absence of hypocretin-1 in the cerebrospinal fluid. We discuss potential pathophysiological implications as well as symptomatic treatment options.

Neurotrophic factor expression in three infants with Ondine's curse.

This study investigates the expression of some neurotrophic factors (brain-derived neurotrophic factor, glial-derived neurotrophic factor, and nerve growth factor) in the cerebrospinal fluid of infants suffering from idiopathic congenital central hypoventilation syndrome and determines their correlations with this syndrome. Cerebrospinal fluid samples were collected from three infants suffering from idiopathic congenital central hypoventilation syndrome and 15 control subjects with obstructive hydrocephalus to measure the expression of brain-derived neurotrophic factor, glial-derived neurotrophic factor, and nerve growth factor using an immunoenzymatic assay. In the cerebrospinal fluid of patients, analysis of neurotrophic factors expression indicated a reduction, not statistically significant, of brain-derived neurotrophic factor compared with the mean level of the control group (1554 pg/mL, 1509 pg/mL, and 1582 pg/mL respectively, in comparison to 1954 +/- 103 pg/mL), whereas nerve growth factor and glial-derived neurotrophic factor did not undergo significant variations in either group. Neurotrophic factors, namely brain-derived neurotrophic factor, regulate the maturation and differentiation of respiratory neurons. The reduced expression of brain-derived neurotrophic factor in the cerebrospinal fluid samples of infants with Ondine's curse, although not statistically significant, is suggestive of a dysregulation in the brain-derived neurotrophic factor synthesis that could play an important role in the breathing disorders observed in patients with idiopathic congenital central hypoventilation syndrome.