**3. Cellular / molecular factors**

Analysis of synovial tissue specimens taken from affected knee joints reveals a typical finding of 2 distinct cell types: Type A cells contain Golgi complexes and resemble macrophages, whose function is predominately one of phagocytosis, and Type B cells contain a proper nucleus and rough endoplasmic reticulum, whose function is mainly protein synthesis (Rooney et al 1988). The histological analysis of affected tissue in the cervical spine demonstrates that the histopathological process of late rheumatoid progression may be different compared with that of the joints of the appendicular skeleton (O'Brien et al 2002). Analysis of chronic rheumatoid disease in the craniocervical junction reveals ligamentous and bony destruction allied with a replacement of rheumatoid synovium of atlantoaxial and subaxial joints with fibrous tissue. Gross mechanical instability at the heavy-weight-bearing craniocervical junction and atlantoaxial joints is caused by bony destruction and replacement of ligamentous structures, as opposed to the acute rheumatoid inflammatory processes commonly seen in appendicular joints. Craniocervical junction chronic rheumatoid arthritis may be considered to be a progressive mechanical disabling process, as opposed to the metabolically active prevalent in other locations.

disease of the cervical spine remains a challenging opponent for the modern day spine surgeon. The challenge lies in both the poor general medical condition of most rheumatoid patients with cervical spine dysfunction (Skues & Welchew 1993), and the bone destruction and ligamentous laxity that make instrumentation difficult in all but the most specialists of practices. A predilection for developing post-operative infections also contributes to an understandable wariness on the part of non-specialist neurosurgical/orthopaedic surgeons of embarking on major instrumentation without having ready access to the necessary back-

**2. Epidemiology of upper cervical spine involvement in rheumatoid disease**  Rheumatoid arthritis has a mean age of onset at 50 years old. The first documented case of rheumatoid involvement of the cervical spine was reported by Garrod, who noted clinical evidence of rheumatoid disease in the cervical spines of 36% of his 500 rheumatoid patients. It is a ubiquitous condition, and has a male: female incidence ratio of 1:3. Initiation of combination drug therapy of disease-modifying-agents (e.g. sulfasalazine, methotrexate, hydroxychloroquine, prednisolone) at an early stage in the disease process, before extensive cervical or systemic damage has been caused, has been shown to retard the development of upper cervical subluxations (Neva et al 2000). It has been estimated that cervical involvement occurs in over 60% of rheumatoid cases (Dickman et al 1997), with atlantoaxial subluxation occurring in almost 70% of these cases (Boden et al 1993). Whilst basilar invagination and cranial settling are less commonly seen, the associated neurological deficits can be dire, with wide ranges of associated neurological deficits are reported (Zeidman & Ducker 1994), resulting in an estimated cost per case to the taxpayer of over €9500 per annum in late cases (Westhovens et al 2005). Initiation of combination drug therapy of disease-modifying-agents (e.g. sulfasalazine, methotrexate, hydroxychloroquine, prednisolone) at an early stage in the disease process, before extensive cervical or systemic damage has been caused, has been shown to retard the development of upper cervical

Analysis of synovial tissue specimens taken from affected knee joints reveals a typical finding of 2 distinct cell types: Type A cells contain Golgi complexes and resemble macrophages, whose function is predominately one of phagocytosis, and Type B cells contain a proper nucleus and rough endoplasmic reticulum, whose function is mainly protein synthesis (Rooney et al 1988). The histological analysis of affected tissue in the cervical spine demonstrates that the histopathological process of late rheumatoid progression may be different compared with that of the joints of the appendicular skeleton (O'Brien et al 2002). Analysis of chronic rheumatoid disease in the craniocervical junction reveals ligamentous and bony destruction allied with a replacement of rheumatoid synovium of atlantoaxial and subaxial joints with fibrous tissue. Gross mechanical instability at the heavy-weight-bearing craniocervical junction and atlantoaxial joints is caused by bony destruction and replacement of ligamentous structures, as opposed to the acute rheumatoid inflammatory processes commonly seen in appendicular joints. Craniocervical junction chronic rheumatoid arthritis may be considered to be a progressive mechanical disabling process, as opposed to the

up should complications arise (Lidgran 1973, Grennan et al 2001).

subluxations (Neva et al 2000).

**3. Cellular / molecular factors** 

metabolically active prevalent in other locations.
