Higher Orexin A levels in lumbar compared to ventricular CSF: a study in idiopathic normal pressure hydrocephalus

Orexin A (ORX-A) is implicated in the regulation of various physiological processes, including sleep/wake cycles and reward/motivation. The hypothalamic ORX-A neurons project throughout the brain and spinal cord. In the present study we established and compared ORX-A levels in lumbar and ventricular cerebrospinal fluid (CSF) samples, drawn from idiopathic normal pressure hydrocephalus (INPH) patients, during respectively, lumbar puncture and shunt placement. Ventricular and lumbar CSF levels of total protein and of the dopamine, serotonin and norepinephrine metabolites HVA, 5-HIAA and MHPG respectively, were also estimated. ORX-A was quantified using a commercially available radioimmunoassay kit. Neurotransmitter metabolites were quantified by high performance liquid chromatography. Expectedly, HVA and 5-HIAA levels were significantly higher and total protein levels lower in ventricular compared to lumbar CSF while there were no differences in MHPG levels. However, in contrast to HVA and 5-HIAA and similar to total protein, lumbar ORX-A levels were significantly higher than ventricular levels. The higher lumbar compared to ventricular ORX-A levels may reflect elevated contributions from the spinal cord. The finding of a ventriculo-lumbar difference for ORX-A should be considered in studies utilizing its CSF levels in assessing Orexin system status.