Cerebrospinal fluid orexin in aneurysmal subarachnoid haemorrhage - a pilot study

The hypothalamus, a vital regulator of multiple physiologic functions, is the principal source of the neuropeptide orexin, which is thought to regulate the sleep-wake cycle. As hypothalamic damage may result from aneurysmal subarachnoid haemorrhage (SAH) and be associated with a depressed conscious level, we sought to investigate whether orexin levels reflected the severity of the ictus and were of any prognostic value in SAH. CSF orexin levels from 15 patients with aneurysmal SAH were analysed for up to 14 days. The correlation between orexin and GCS, WFNS grade, Fisher grade, GOS at 6 months and hydrocephalus were ascertained. Orexin levels in 5 patients with normal pressure hydrocephalus were used as controls. Patients with GCS less than 8 on admission had undetectable orexin whilst those with a GCS of 8 or greater had measurable orexin (p < 0.05). CSF orexin levels appear to correlate with conscious level and might be a valid indicator of hypothalamic injury. As some adverse sequelae of SAH are due to hypothalamic damage, pharmacological manipulation of orexinergic neuronal pathways could lead to exciting therapeutic options in the future.