title: Elevated levels of phosphorylated neurofilament heavy subunit in the cerebrospinal fluid of patients with lumbar spinal stenosis: preliminary findings.
abstract: BACKGROUND
  The phosphorylated neurofilament heavy subunit (pNfH) is an axon fiber structural protein that is released into the cerebrospinal fluid (CSF) after nerve damage. Although the previous studies have reported elevated CSF levels of pNfH in various neurological diseases, including amyotrophic lateral sclerosis, these levels have not been examined in patients with spinal stenosis.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the CSF levels of pNfH in patients with lumbar spinal stenosis (LSS) and to examine the relationship between CSF levels of pNfH and the severity of LSS.
  
  
  METHODS
  This is a prospective observational study.
  
  
  METHODS
  We included consecutive patients with LSS who were undergoing myelography for preoperative evaluation. The CSF samples from patients with idiopathic scoliosis were used as the controls.
  
  
  METHODS
  Physiological measures: CSF levels of pNfH were measured using an enzyme-linked immunosorbent assay. The Zurich Claudication Questionnaire (ZCQ) and the Numerical Rating Scale (NRS) for sciatic pain were used to assess the clinical severity of LSS, and patients were grouped into tertiles according to their symptom severity and pain grading. Axial magnetic resonance imaging was used to evaluate the morphological severity of LSS, and patients were classified into three groups based on their morphological grading (using the CSF/rootlet ratio).
  
  
  METHODS
  Analysis of variance was used to examine the relationship between the CSF levels of pNfH and the severity of LSS.
  
  
  RESULTS
  Thirty-three patients with LSS were included (13 men and 20 women and mean age 73.2 [range 58-88] years). Most patients (n=32) were positive for pNfH in their CSF (mean 1,344 [149-9,250] pg/mL), whereas all control subjects were negative for pNfH in their CSF. Regarding the association with clinical severity, patients in the third tertiles of ZCQ and NRS tended to have higher levels of pNfH compared with the other groups. There was no association between the CSF level of pNfH and the morphological severity of LSS.
  
  
  CONCLUSIONS
  This study detected elevated pNfH levels in the CSF of patients with LSS. Patients with severe clinical symptoms were more likely to exhibit high levels of pNfH. Our results indicate the potential usefulness of pNfH as a biomarker for compressive spinal disorders.
authors: Department of Orthopaedic Surgery, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan.
authors: Junichi
authors: J
authors: Ohya
authors: Department of Orthopaedic Surgery, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan. Electronic address: chikuda-tky@umin.ac.jp.
authors: Hirotaka
authors: H
authors: Chikuda
authors: Department of Orthopaedic Surgery, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan.
authors: So
authors: S
authors: Kato
authors: Department of Orthopaedic Surgery, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan.
authors: Kentaro
authors: K
authors: Hayakawa
authors: Department of Orthopaedic Surgery, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan.
authors: Hiroyuki
authors: H
authors: Oka
authors: Department of Orthopaedic Surgery, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan.
authors: Katsushi
authors: K
authors: Takeshita
authors: Department of Orthopaedic Surgery, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan.
authors: Sakae
authors: S
authors: Tanaka
authors: Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, 4-1, Namiki, Tokorozawa, Saitama, Japan.
authors: Toru
authors: T
authors: Ogata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D012720:Severity of Illness Index; D013130:Spinal Stenosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; C051774:neurofilament protein H
keywords: Biomarker; Cerebrospinal fluid; Diagnosis; Lumbar spinal stenosis; Outcome; Phosphorylated neurofilament heavy subunit