Background and purpose Anti-beta2-glycoprotein I (anti-beta2-GPI) antibodies are part of the heterogeneous family of antiphospholipid antibodies and seem to be present in various neurological manifestations in addition to antiphospholipid syndrome (APS). Our objective was to analyse the clinical, radiological and therapeutic characteristics of neurological patients with positive anti-beta2-GPI antibodies and without the Sapporo criteria for APS. Methods The medical records were retrospectively reviewed of 28 consecutive patients hospitalized in the Neurology Department of Strasbourg University Hospital, France, in whom anti-beta2-GPI antibodies (immunoglobulin G and/or immunoglobulin M) were positive and other antiphospholipid antibodies negative, from November 2005 to July 2011. Clinical, radiological, biological and therapeutic data and clinical course were studied. Results Positive anti-beta2-GPI antibodies were present in 28 patients. The predominant physiopathological process was mainly inflammatory (25% with myelitis, 14.3% with optic neuritis) or vascular (14.3% with cerebral ischaemia, 7.1% with cerebral vasculitis). Brain magnetic resonance imaging was performed in 89.3% of patients: atypical lesions were observed in 44% and typical inflammatory and vascular lesions in 16% and 12%, respectively. Conclusion The anti-beta2-GPI antibody seems to be involved in two types of neurological disease: vascular or inflammatory 'multiple sclerosis-like' disease. These two types of patients frequently develop an autoimmune disease (multiple sclerosis, systemic lupus erythematosus, APS). However, a large proportion of the patients had an undefined profile with aspecific cerebral lesions and required monitoring. This study raises questions about a separate entity at the border between APS and multiple sclerosis which remains to be better defined in a larger cohort. PUBLICATION ABSTRACT