Objective: Oligoclonal band (OCB)-negative MS is well-recognised but uncommon, studied in only a few, usually small case series. These reach differing conclusions on whether its clinical features or course differ from OCB-positive disease. We hypothesised that a definitive study would not only be of clinical and prognostic value but also potentially offer information about the possible role of CSF oligoclonal immunoglobulins in MS disease processes.
Methods: We utilised a collaborative cohort of well-documented patients in southwest England and south Wales to identify and analyse a large group of patients with OCB-negative MS and make comparisons with age- and sex-matched OCB-positive controls.
Results: An approximate minimum 3% of patients with MS were OCB-negative. They were significantly more likely to exhibit neurological or systemic clinical features atypical for MS (headaches, neuropsychiatric features and skin changes). Non-specific MRI, blood and (other) CSF abnormalities were also more common, emphasising the need for continued diagnostic vigilance – although the incautious application of McDonald diagnostic criteria in OCB-negative cases renders categorisation as “definite” MS more likely. Studying the uniformly-assessed Cardiff group (69 patients), we found the prognosis for neurological disability was significantly better for OCB-negative cases. The age-adjusted hazard-ratio for OCB-negative and OCB-positive subjects to reach DSS4 and DSS6 was respectively 0.60 (95% CI 0.39-0.93, p=0.02) and 0.51 (95% CI 0.27-0.94, p=0.03).
Interpretation: There are clear clinical differences between OCB-negative and OCB-positive MS, in particular a better prognosis for disability. This is consistent with a secondary but nonetheless contributory role in disease process for intrathecally-synthesised immunoglobulins.