Decreased Cerebrospinal Fluid Orexin-A (Hypocretin-1) Concentrations in Patients after Generalized Convulsive Status Epilepticus

Abstract

The effects of status epilepticus on the orexin/hypocretin system have yet to be investigated. The present study aimed to assay orexin-A/hypocretin-1 in the cerebrospinal fluid (CSF) of patients after generalized convulsive status epilepticus (GCSE). The study groups included 20 GCSE patients, 24 patients diagnosed with epilepsy but remaining in remission (ER), and 25 normal controls (CTR). Diagnostic lumbar puncture was performed in GCSE patients within 3-10 days of seizure cessation, as well as in the ER and to CTR subjects. Among all GCSE patients, the outcome was graded according to the modified Rankin Scale (mRS) at 1-month follow-up. Orexin-A levels were measured in unextracted CSF samples, using a commercial radioimmunoassay. There was a significant overall difference in median CSF orexin-A concentrations between GCSE, RE, and CTR patients (p < 0.001). The lowest concentrations were noted in the GCSE group compared to ER (p < 0.001) or CTR (p < 0.001). CSF orexin-A levels in GCSE patients inversely correlated with clinical outcome as assessed on the mRS at 1-month follow-up (r = -0.55; p = 0.1). In conclusion, CSF orexin-A levels may serve as a biomarker of increased turn-over of the peptide or post-SE neuronal damage, and implicates the orexin system in the pathogenesis of SE.

Keywords: biomarker; cerebrospinal fluid; generalized convulsive status epilepticus; hypocretin 1; orexin-A.

Figure 1

(A) Cerebrospinal fluid (CSF) orexin-A levels (pg/mL) in controls (CTR), epilepsy patients in remission (ER), and patients with generalized convulsive status epilepticus (GCSE) (GCSE vs. CTR, p < 0.001; GCSE vs. ER, p < 0.001; ER vs. CRT, p > 0.05); *** p < 0.001; n.s. = not significant. (B) Cerebrospinal fluid (CSF) orexin-A levels (pg/mL) correlated with modified Rankin Score (mRS) in patients with GCSE (Spearman, r = −0.55; p = 0.01).