Search results
The literature search identified 12,249 citations with 412 duplicates. Titles or abstracts
(if available) were screened for eligibility, yielding 126 citations for full text
review. Twelve studies were case reports. Twenty-nine studies were editorials or reviews.
Eleven studies did not report on the rate or progression of cervical complications.
Eleven studies examined patients with severe neck complaints or suspected/known cervical
instabilities. Six excluded studies examined the prevalence of cervical instabilities
in RA but had a sample size of less than 100. Two articles were identified by hand-searching
key references. In total, 67 articles were excluded, leaving 59 studies to be included
in our meta-analysis (Figure 1).
Figure 1. (A) Search strategy for articles and (B) Funnel plots to determine if there was publication bias. Funnel plot 1: Graph of
sample size of individual study (x-axis) and its respective prevalence of anterior
atlanto-axial subluxations (y-axis). Funnel plot 2: Graph of sample size of individual
study (x-axis) and its respective prevalence of rheumatoid arthritis (RA)-related
cervical changes (y-axis). Funnel plot 3: Graph of sample size of individual study
(x-axis) and its respective prevalence of vertical atlanto-axial subluxations (y-axis).
Funnel plot 4: Graph of sample size of individual study (x-axis) and its respective
prevalence of subaxial subluxations (y-axis). Funnel plot 5: Graph of sample size
of individual study (x-axis) and its respective prevalence of cervical myelopathy
(y-axis).
Description of the included studies and participants
Fifty studies reported on the prevalence of cervical instabilities. Three studies
were published in the 1960s with 533 participants (4% of pooled study population),
nine studies in the 1970s with 2,798 participants (23%), nine studies in the 1980s
with 1,449 participants (12%), nine studies in the 1990s with 1,653 participants (14%),
13 studies in the 2000s with 3,777 participants (31%), and seven studies in the 2010s
with 2,012 participants (16%) 2]-4],7]-12],15],17],21]-59]. The total number of enrolled patients was 12,222. Major world regions were represented.
Six studies were from the United States, including 855 participants (7% of pooled
study population) 3],15],17],21],33],35]. Twenty-six studies were from Europe with a total of 7,315 participants (60%) 2],4],7],10],22]-25],27]-31],34],37],38],40],43]-46],49]-52],59]. Sixteen studies were conducted in Asia, totaling 3,662 participants (30%) 8],9],12],26],32],39],41],42],47],48],53]-58]. An additional study compared a Malaysian cohort with a British cohort with a total
of 140 patients 36]. One study was from Africa and included 250 people (2%) 11]. The average female representation was 75%. The mean age at the time of outcome assessment
was 58 years old (range of 33 to 69 years), and the mean disease duration was 12 years
(range of 2 to 30 years).
Twenty studies were included for analyzing the progression of cervical instabilities.
Data were obtained from 12 of the studies described above as well as nine additional
studies 7],8],14]-16],22],23],25],29],32],42],55],56],60]-66]. The number of enrolled participants was 2,157, and the average follow-up was 6 years
(range of 3 to 10 years). Eighty percent of the participants were female. The mean
age and disease duration at the time of final assessment were 60 years (range of 50
to 67 years) and 15 years (range of 7 to 30 years), respectively.
Across all studies, the median number of items fulfilled on the STROBE checklist was
16 (range of 11 to 19) and reporting was improved in more recent studies. Characteristics
of the included studies are shown in Tables 1 and 2.
Table 1. Characteristics of 50 studies reporting prevalence of cervical subluxations
Table 2. Characteristics of 20 studies reporting progression of cervical subluxations
Prevalence of any rheumatoid arthritis-related changes, cervical subluxations, and
cervical myelopathy
Twelve studies reported the prevalence of any RA-related cervical changes, not limited
to subluxations. Out of 3,559 patients, 1,597 (45%) were found to have one or more
of those radiographic changes. There were no significant changes over time of publication
(P = 0.71).
AAS was the most common subluxation found in our study. Twenty-seven percent (2,737
patients) had aAAS. Lateral AAS was reported in 68 patients (0.7%). Posterior and
rotatory AASs were found in 21 (0.2%) and 10 (0.1%), respectively. In comparisons
among different world regions, the prevalences of aAAS were 25%, 27%, and 31% for
Europe, North America, and Asia, respectively (P = 0.13). The prevalences of aAAS were 36% in the 1970s and earlier (95% CI 30% to
42%), 36% in the 1980s (95% CI 23% to 42%), 32% in the 1990s (95% CI 20% to 44%),
and 24% in the 2000s (95% CI 13% to 36%) (P = 0.04). VS and SAS had comparable prevalence rates. VSs were reported in 831 of
7,675 patients with RA with a prevalence of 11% (95% CI 10% to 19%); SAS occurred
in 838 of 6,672 patients with RA (13%; 95% CI 12% to 20%). No significant temporal
changes were noted for either VS or SAS (P = 0.17 and P = 0.49, respectively).
Twenty-three studies with 5,106 patients with RA reported on cervical myelopathy.
Two hundred seventy-one patients (prevalence of 5%) had observed neurological deficits
corresponding to Ranawat Cervical Myelopathy Classification II and above (95% CI 3%
to 9%) 67]. We did not observe a significant change over time (P = 0.22). In terms of serious neurological complications, nine patients (0.2%) were
observed to develop paraplegia. Ten additional patients (0.2%) had symptoms of possible
brainstem involvement, including nausea, vertigo, or drop attacks.
Progression of cervical subluxations and cervical myelopathy
Sixteen studies reported on the progression of 945 aAAS lesions. After 10,046 person-years,
219 of the existing subluxations had an increase in altanto-dental interval on radiography.
Therefore, on average, 4 out of 100 existing aAAS lesions progressed per year. As
for VS, 148 of 407 known lesions had radiographic progression, following 8,468 person-years.
This corresponded to a progression rate of 6 per 100 lesions per year. Lastly, only
5 studies reported on SAS progression. A total of 46 out of 208 existing lesions progressed
during the 4,781 person-years of follow-up. Therefore, the rate of SAS progression
was 3 lesions per 100 existing lesions per year. The rate of progression for these
subluxations was not found to be significantly different over time (aAAS, P = 0.99; VS, P = 0.49). Owing to the small number of studies, the rate of SAS progression over time
was not analyzed.
Cervical myelopathy was assessed in 1,310 patients with RA with 9,131 person-years
of follow-up. A total of 772 people had AAS, VS, SAS, or a combination of subluxations.
Seventy-nine had new or progressive cervical myelopathy at the end of follow-up. We
thus calculated a rate of 1.5 new/progressive cervical myelopathies per 100 patients
with known cervical subluxations per year. Over time, the rates were 0.8, 2.1, 1.3,
and 2.4 for the 1970s, 1980s, 1990s, and 2000s, respectively (P = 0.05).