The Emerging Role of Hypocretin (Orexin-A) in the Developing Central Nervous System

Extract

The normal values for cerebrospinal fluid (CSF) hypocretin-1 in adults are predictable and stay within a range of 280 ± 33 pg/mL.¹ Levels below 110 pg/mL are typically observed in patients with narcolepsy-cataplexy. Reference values for hypocretin during the neonatal period and early infancy have, however, not been standardized, and it is not known if they change with gestational age or maturation.

In this issue of SLEEP, Aran and colleagues² report on cerebrospinal fluid (CSF) levels of hypocretin-1 (orexin-A) measured during early infancy. They gathered an initial pool of 284 infants (preterm and full term) and 35 older children aged 0.5-13 years of age who had undergone lumbar puncture for presumed sepsis. Of those younger than 4 months of age, 43 were preterm (28-34 weeks post-conceptional age), while 52 had been born at full term. From this pool, 108 neurologically intact subjects were selected for further study—there were 95 infants less than 4 months age, while 13 were older children. In order to be categorized as “neurologically intact,” the patient had to have no medical problem other than being premature, possess a normal neurological examination, have normal blood and cerebrospinal fluid laboratory tests, and maintain a normal examination at 48 hours post-lumbar puncture. Forty-nine of the 108 subjects had lumbar punctures performed during the first 24 hours after birth, with 19/49 having undergone the procedure within the first hour. Cerebrospinal fluid hypocretin-1 levels were measured by radioimmunoassay. For infants of 28-34 weeks gestation, the hypocretin-1 levels were 314 ± 65 pg/ mL, increasing linearly to 476 ± 72 pg/mL by 2-4 months after age, and being higher than those in the 0.5-13 year age group (353 ± 78 pg/mL; P = 0.0001).