Accelerated development of cervical spine instabilities in rheumatoid arthritis: a prospective minimum 5-year cohort study

Abstract

Objective: To clarify the incidence and predictive risk factors of cervical spine instabilities which may induce compression myelopathy in patients with rheumatoid arthritis (RA).

Methods: Three types of cervical spine instability were radiographically categorized into "moderate" and "severe" based on atlantoaxial subluxation (AAS: atlantodental interval >3 mm versus ≥10 mm), vertical subluxation (VS: Ranawat value <13 mm versus ≤10 mm), and subaxial subluxation (SAS: irreducible translation ≥2 mm versus ≥4 mm or at multiple). 228 "definite" or "classical" RA patients (140 without instability and 88 with "moderate" instability) were prospectively followed for >5 years. The endpoint incidence of "severe" instabilities and predictors for "severe" instability were determined.

Results: Patients with baseline "moderate" instability, including all sub-groups (AAS(+) [VS(-) SAS(-)], VS(+) [SAS(-) AAS(±)], and SAS(+) [AAS(±) VS(±)]), developed "severe" instabilities more frequently (33.3% with AAS(+), 75.0% with VS(+), and 42.9% with SAS(+)) than those initially without instability (12.9%; p<0.003, p<0.003, and p = 0.061, respectively). The incidence of cervical canal stenosis and/or basilar invagination was also higher in patients with initial instability (17.5% with AAS(+), 37.5% with VS(+), and 14.3% with SAS(+)) than in those without instability (7.1%; p = 0.028, p<0.003, and p = 0.427, respectively). Multivariable logistic regression analysis identified corticosteroid administration, Steinbrocker stage III or IV at baseline, mutilating changes at baseline, and the development of mutilans during the follow-up period correlated with the progression to "severe" instability (p<0.05).

Conclusions: This prospective cohort study demonstrates accelerated development of cervical spine involvement in RA patients with pre-existing instability--especially VS. Advanced peripheral erosiveness and concomitant corticosteroid treatment are indicators for poor prognosis of the cervical spine in RA.

Figure 1. Numbers of patients enrolled, followed, and lost to follow-up with the baseline proportion of “classical” and “definite” rheumatoid arthritis (RA) in the American Rheumatism Association 1958 criteria and the >5-year incidence of cervical spine surgery for myelopathy.

Patients were grouped by the type of pre-existing cervical spine involvement: no instability, atlantoaxial subluxation (AAS) alone (shown as AAS⁺), vertical subluxation (VS) without subaxial subluxation (SAS) but with or without AAS (shown as VS⁺), and SAS with and/or without either AAS and/or VS (shown as SAS⁺) and by the level of severity—“moderate” and “severe”.

Figure 2. Baseline and >5-year distributions of radiographic parameters for upper cervical spine involvement, the atlantodental interval (ADI), Ranawat value, and space available for the spinal cord (SAC) at C1–C2, in 228 patients without “severe” cervical spine instability at baseline.

Patients were grouped by pre-existing cervical spine involvement: no instability, “moderate” atlantoaxial subluxation (AAS) alone (shown as AAS⁺), “moderate” vertical subluxation (VS) without subaxial subluxation (SAS) but with or without AAS (shown as VS⁺), and “moderate” SAS with and/or without either AAS and/or VS (shown as SAS⁺). Data are expressed as mean ± standard deviation. **p<0.01 by the paired t-test. ^†p<0.05, ^††p<0.01 by the Wilcoxon signed-rank test because of the small number of cases.