Prospective Study on Serum Protein Biomarkers for Diagnosis and Prognosis in Degenerative Cervical Myelopathy

Introduction: Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic spinal cord injury worldwide. Many of the early symptoms of DCM are subtle, difficult to confirm on clinical examination, and may be confounded by co-morbid conditions. Delays in diagnosis are common in DCM and there is a need for additional objective assessments of spinal cord structure and function. The objective of this study was to profile serum protein biomarkers in DCM and determine their potential diagnostic and prognostic utility in DCM.

Methods: Patients clinically diagnosed with DCM (n=20) and scheduled for decompressive surgery were prospectively enrolled from July 2022 to August 2023. Serum neuronal and inflammatory proteins were quantified before surgery and at 3 months after surgery for DCM patients. Serum protein levels were compared between DCM patients and healthy controls (n=10). Multivariable regressions were used to estimate associations with different biomarkers after variable selection.

Results: DCM patients (10 males, 10 females) had a median age 70 years and healthy controls (5 males, 5 females) had a median age 65 years. Pre-surgical NfL (30.2 vs 11.2 pg/ml, p=0.01) and IL-6 (2.9 vs 1.2, p=0.003) were significantly higher in DCM patients compared to controls. Pre-surgical NfL, IL-6 and BDNF best differentiated DCM and controls (p < 0.001). The combined panel of NfL, IL-6, and BDNF demonstrated an AUC of 0.83 (95% CI 0.68-0.98). At 3 months after surgery, serum BDNF (p=0.001), AB-42 (p=0.042) and TNFa (p=0.007) were significantly increased compared to pre-surgical values. Pre-surgical serum NfL was significantly associated with improvement in pinch strength after surgery (p=0.03). Inflammatory biomarkers (IL-6, IL-10, IL-22) were linked to postoperative improvement in the neck pain-related disability, while neuronal biomarkers (AB40, BDNF, Tau) were linked to improvement in neurological function.

Conclusion : Pre-surgical serum levels of NfL, IL-6, and BDNF show potential as diagnostic markers for DCM. Pre-surgical serum biomarkers of neuronal damage and inflammation predict early post-surgical functional outcomes in DCM.