Clinical biomarkers differentiate myelitis from vascular and other causes of myelopathy

Abstract

Objective: To assess the predictive value of the initial clinical and paraclinical features in the differentiation of inflammatory myelopathies from other causes of myelopathy in patients with initial diagnosis of transverse myelitis (TM).

Methods: We analyzed the clinical presentation, spinal cord MRI, and CSF features in a cohort of 457 patients referred to a specialized myelopathy center with the presumptive diagnosis of TM. After evaluation, the myelopathies were classified as inflammatory, ischemic/stroke, arteriovenous malformations/fistulas, spondylotic, or other. A multivariable logistic regression model was used to determine characteristics associated with the final diagnosis and predictors that would improve classification accuracy.

Results: Out of 457 patients referred as TM, only 247 (54%) were confirmed as inflammatory; the remaining 46% were diagnosed as vascular (20%), spondylotic (8%), or other myelopathy (18%). Our predictive model identified the temporal profile of symptom presentation (hyperacute <6 hours, acute 6-48 hours, subacute 48 hours-21 days, chronic >21 days), initial motor examination, and MRI lesion distribution as characteristics that improve the correct classification rate of myelopathies from 67% to 87% (multinomial area under the curve increased from 0.32 to 0.67), compared to only considering CSF pleocytosis and MRI gadolinium enhancement. Of all predictors, the temporal profile of symptoms contributed the most to the increased discriminatory power.

Conclusions: The temporal profile of symptoms serves as a clinical biomarker in the differential diagnosis of TM. The establishment of a definite diagnosis in TM requires a critical analysis of the MRI and CSF characteristics to rule out non-inflammatory causes of myelopathy.

Classification of evidence: This study provides Class IV evidence that for patients presenting with myelopathy, temporal profile of symptoms, initial motor examination, and MRI lesion distribution distinguish those with inflammatory myelopathies from those with other causes of myelopathy.

Figure 1. Individual clinical predictors for each diagnostic category

Odds ratio estimates and 95% confidence intervals (CI) are shown for each diagnostic category relative to the inflammatory group; statistically significant associations (p < 0.05) are highlighted in red. AVF = arteriovenous fistulas; AVM = arteriovenous malformations; Gad+ = gadolinium-enhanced lesions; IgG = immunoglobulin G; LE = longitudinally extensive lesions; OCB = oligoclonal bands; R = reference group; VM = vascular myelopathy.

Figure 2. Spinal cord MRI lesion patterns in patients with myelopathies

(A) Heatmap representation of lesion distribution frequency for each diagnostic category. The y axis represents sagittal localization based on using the vertebral levels (C2–L2) and the x–z axes represent the axial distribution of the lesion as affecting the anterior, central, lateral, or posterior regions of the spinal cord. Frequency for each localization ranges from 0% (yellow) to 100% (bright red). (B) MRI examples in the different myelopathy diagnostic categories. (B.a) Cervical spine MRI from a patient with idiopathic inflammatory myelopathy reveals signal intensity abnormality in T2-weighted sequences and enhancement in the postero-lateral region of the cervical cord (T1-weighted + gadolinium [Gad]). (B.b) Cervical spine MRI from a patient with vascular myelopathy (VM)–ischemic/stroke shows an anterior signal intensity abnormality in T2-weighted sequences in both sagittal and axial views, which appears unenhanced in T1-weighted sequences + Gad. (B.c) Thoracic MRI in a patient with a VM–arteriovenous fistula (AVF) seen as a longitudinal extensive myelopathy and diffuse intra-axial enhancement in the central cord; there are enlarged vessels in the dorsal surface of the cord (arrow). (B.d) Cervical spine MRI in a patient with spondylotic myelopathy shows signal intensity abnormality in T2-weighted sequences and patchy enhancement (T1 + Gad) in the central cervical cord. AVM = arteriovenous malformations.