Cerebrospinal Fluid Myelin Basic Protein as a Prognostic Biomarker in Dogs with Thoracolumbar Intervertebral Disk Herniation

Abstract

Background: Release of myelin basic protein (MBP) into the cerebrospinal fluid (CSF) is associated with active demyelination and correlates with outcome in various neurological diseases.Hypothesis/Objectives: To describe associations among CSF MBP concentration, initial neurological dysfunction, and long-term ambulatory outcome in dogs with acute thoracolumbar intervertebral disk herniation (IVDH).Animals: Five hundred and seventy-four dogs with acute thoracolumbar IVDH and 16 clinically normal dogs. Methods: Prospective case series clinical study. Signalment, initial neurological dysfunction as determined by a modified Frankel score (MFS), and ambulatory outcome at 43-month follow-up were recorded. Cisternal CSF MBP concentration was determined by an ELISA. Associations were estimated between CSF MBP concentration and various clinical parameters.Results: Dogs with thoracolumbar IVDH that did not ambulate at follow-up had a higher CSF MBP concentration (median, 3.56 ng/mL; range, 0.59-51.2 ng/mL) compared with control dogs (median, 2.22 ng/mL; range, 0-3.82 ng/mL) (P 5 .032). A CSF MBP concentration of !3 ng/mL had a sensitivity of 78% and specificity of 76% to predict an unsuccessful outcome based on receiver-operating characteristics curve analysis (area under the curve 50.688, P 5 .079). Affected dogs with a CSF MBP concentration !3 ng/mL had 0.09 times the odds of ambulation at follow-up compared with affected dogs with CSF MBP concentration o3 ng/mL when adjusted for initial MFS (95% confidence interval 0.01-0.66, P 5 .018).Conclusions and Clinical Importance: These results would suggest that CSF MBP concentration may be useful as an independent prognostic indicator in dogs with thoracolumbar IVDH.

Associations between cerebrospinal fluid biomarkers and long-term neurologic outcome in dogs with acute intervertebral disk herniation

“…Both the MFS 23 and CSF MBP concentration 13 have been previously associated with functional recovery in dogs with thoracolumbar IVDH and were shown via the logistic regression analysis to be independently related to outcome within the dogs in the present study; details of the findings regarding MBP concentration have been communicated in another report 13 about the same group of dogs. The collective impact of CSF CK activity, CSF MBP concentration, and MFS depends on case characteristics.…”

“…By use of this value and a previously reported 13 cutoff value for CSF MBP concentration of 3 ng/mL in the same group of dogs, both CSF CK activity and MBP concentration were significant predictors of long-term outcome in dogs with thoracolumbar IVDH (Table 4). Table 3-Biomarker concentrations and activities in plasma and CSF samples collected from 54 dogs with thoracolumbar IVDH (confirmed at surgery) and 16 control dogs without thoracolumbar IVDH at a single referral hospital.…”

“…13 Owner consent was obtained prior to dog enrollment by use of standard documents approved by the Clinical Research Review Committee. To be included in the affected group, dogs had to meet certain criteria as follows: signs of nonambulatory paraparesis or paraplegia with a ≤ 7-day history of neurologic impairment, intervertebral disk-associated spinal cord compression located between vertebral articulations at T3 through L5, and confirmation of disk herniation during surgery or necropsy.…”

“…In addition, 2 to 4 additional aliquots (200 to 300 µL) of CSF from each dog were frozen at -80°C immediately after collection for determination of MBP concentration as previously described. 13 Samples were analyzed within 1 hour after collection by use of an automated chemistry analyzer. Variables of interest included nucleated cell count; lactate, calcium, glucose, and total protein concentrations; and CK and AST activities.…”

“…Findings of that study revealed that each unit increase in the T2W length ratio was associated with a nearly 2-fold reduction in the odds of recovery, independent of neurologic assessment. More recently, dogs with acute thoracolumbar IVDH that had CSF concentrations of MBP ≥ 3 ng/mL were reported 13 to have 0.09 times the odds of ambulation at a follow-up examination, compared with affected dogs that had CSF concentrations of MBP less than this cutoff value. Other investigators 14 have shown that CSF pleocytosis and abnormally high CSF protein concentration are associated with severe physical examination-based features of spinal cord injury in dogs with thoracolumbar IVDH.…”