Combination of serum phosphorylated neurofilament heavy subunit and hyperintensity of intramedullary T2W on magnetic resonance imaging provides better prognostic value of canine thoracolumbar intervertebral disc herniation

Abstract

The aim of this study was to evaluate the prognostic value of concurrent measurement of serum phosphorylated neurofilament heavy subunit (pNF-H) concentration and intramedullary T2W hyperintensity in paraplegic to paraplegic dogs. Our hypothesis was that concurrent measurement of these would provide a more accurate prediction of functional outcome in dogs with thoracolumbar intervertebral disc herniation (IVDH). A prospective case-control clinical study was designed using 94 dogs with acute onset of thoracolumbar IVDH. The association of serum pNF-H concentration, T2W hyperintensity on sagittal MRI (T2H/L2), deep pain perception and surgical outcome were evaluated with logistic regression analysis after three months for all 94 surgically treated dogs. Sensitivity to predict non-ambulatory outcome was compared among pNF-H and T2H/L2 and combination of both. Logistic regression analysis indicated that serum pNF-H concentration and T2H/L2 were significantly correlated with surgical outcome (P<0.05); however, deep pain perception was not (P=0.41). The results of logistic regression analysis indicated that the odds ratios of unsuccessful long-term outcome were 2.6 for serum pNF-H concentration, 1.9 for T2H/L2 and 2.3 for deep pain sensation. The sensitivity and specificity to predict non-ambulatory outcome for using serum parameter pNF-H>2.6 ng/ml, using T2H/L2 value of>0.84 and using both serum pNF-H and T2H/L2, were 95% and 75.7%, 65% and 86.5%, and 90.0% and 97.5%, respectively. Therefore, combined measurements of serum pNF-H and T2H/L2 might be useful for predicting long-term outcome in dogs with thoracolumbar IVDH.

Serum phosphorylated neurofilament heavy chain as a diagnostic biomarker for progressive myelomalacia in dogs with thoracolumbar intervertebral disc herniation

“…However, we were not able to detect a difference in serum pNF‐H across groups at baseline, representing the initial 24 hours after injury. While these findings are consistent with a previous study, 15 they are in contrast to earlier reports that found a correlation between serum pNF‐H concentration at the time of hospital admission and functional outcome 13,14 . In particular, serum pNF‐H concentrations at the time of admission observed in these studies ranged from 0 to 60.4 ng/mL in PMM cases, which is markedly higher than values obtained in this study (0‐2.51 ng/mL).…”

“…Specifically, the predictive value of serum pNF‐H concentration of identifying dogs that recover vs dogs that do not after IVDH has been inconsistent across studies, which might be a reflection of the variability in the time of evaluation relative to injury 13‐15 . Moreover, while previous studies have commented that dogs with PMM have elevated serum pNF‐H concentrations relative to other study cohorts, this particular study sample has neither been specifically evaluated as an individual study cohort, nor serially monitored in the acute postoperative period 13‐15 …”

“…Identification of a minimally invasive biomarker that can predict outcome after functionally complete SCI secondary to IVDH would inform owner expectations and facilitate financial and ethical decision‐making. Multiple biomarker candidates have been evaluated in dogs with IVDH, including serum concentrations of glial fibrillary acidic protein, S100β, creatine kinase, lactate, and myelin basic protein 11‐15 . However, none have sufficient prognostic value.…”

“…However, none have sufficient prognostic value. Importantly, no candidate biomarker has been followed longitudinally in PMM cases 11‐16 . Phosphorylated neurofilament‐heavy chain (pNF‐H) has variable success as a predictive biomarker for functional recovery across several species after acute severe SCI 13‐15,17‐20 .…”

“…Importantly, no candidate biomarker has been followed longitudinally in PMM cases 11‐16 . Phosphorylated neurofilament‐heavy chain (pNF‐H) has variable success as a predictive biomarker for functional recovery across several species after acute severe SCI 13‐15,17‐20 . Specifically, the predictive value of serum pNF‐H concentration of identifying dogs that recover vs dogs that do not after IVDH has been inconsistent across studies, which might be a reflection of the variability in the time of evaluation relative to injury 13‐15 .…”