Serum protein biomarkers for degenerative cervical myelopathy: a prospective pilot study

Abstract

Introduction Diagnosis of degenerative cervical myelopathy (DCM) is primarily based on clinical evaluation and evidence of cervical spinal cord compression on conventional MRI. However, delays in diagnosis are common in DCM and there is a need for additional objective assessments of spinal cord structure and function. Serum proteins are increasingly being used as biomarkers for neurological disorders and are promising targets for biomarker discovery in DCM. The objective of this study was to profile serum protein biomarkers in DCM and determine if serum proteins can aid diagnosis and prognosis in DCM. Methods Patients with a clinical diagnosis of DCM and scheduled to undergo decompressive surgery were prospectively enrolled from July 2022 to August 2023. Serum was obtained prior to surgery and at 3 months after surgery. Serum neuronal and inflammatory proteins were quantified using ultrasensitive single-molecular array technology. Serum biomarker concentrations were compared between DCM patients and age- and sex-matched healthy controls. Robust logistic regression was used to determine the panel of serum biomarkers that best differentiated DCM and controls. Serum biomarkers were also related to pre- and post-surgical functional measurements using linear regression. Results Twenty DCM patients (median age 70 years, 10 females) and 10 healthy controls (median age 65 years, 5 females) were enrolled. Pre-surgical NfL (30.2 vs 11.2 pg/ml, p=0.01) and IL-6 (2.9 vs 1.2, p=0.003) was significantly higher in DCM patients compared to controls. Pre-surgical NfL, IL-6 and BDNF best differentiated DCM and controls (p<0.001). At 3 months after surgery, significant increase in serum BDNF (p=0.001), AB-42 (p=0.042) and TNFa (p=0.007) were noted. Pre-surgical serum NfL was significantly associated improvement in pinch strength after surgery (p<0.05). Inflammatory biomarkers were linked to improvement in the neck pain-related disability and upper limb function assessed by the QuickDASH. Conclusion A pre-surgical serum panel of NfL, IL-6 and BDNF may aid in the diagnosis of DCM. Serum NfL is elevated in DCM and is associated with improvement in post-surgical objective measures of upper limb function. Pre-surgical serum neuronal and inflammatory biomarkers predict early post-surgical functional outcomes in DCM.