A 20-year-old woman receiving interferon beta-1a for MS reported a visual field defect in the lower temporal quadrant of the left eye. Examination revealed a normal visual acuity of 20/20 in both eyes. Intraocular pressure was 15 mmHg in the right eye and 17 mmHg in the left eye. Anterior segment examinations were normal in both eyes. Pupils were equal, round and reactive to light with no relative afferent pupillary defect. Fundus examination of the left eye showed ischemic retinal whitening in the supra-nasal area, fluorescein angiography (FA) revealed BRAOs and subtle, segmental arteriolar wall hyperfluorescence (AWH) at the site of BRAO in the late phase. Fundus examination and FA of the right eye were normal. Retrobulbar optic neuritis due to MS was ruled out because the infra-temporal visual field defect reported by the patient corresponded to the area of the ischemic retina due to supra-nasal BRAO. Moreover, the patient did not have reduced visual acuity nor colour vision disturbances, and did not report any pain concomitant to eye movements which is characteristic for retrobulbar optic neuritis in the course of MS. Interferon beta-1a treatment was discontinued after 7 weeks because of its possible prothrombotic effect. A repeat FA performed two weeks later showed reperfusion of the occluded arterioles and resolution of the AWH. The patient had increased thromboembolic risk due to hormonal contraception and cigarette smoking. A full laboratory work-up was done, including tests for connective tissue disease, vasculitis, borrelia, syphilis, human immunodeficiency virus (HIV), herpes simplex virus (HSV), cytomegalovirus (CMV), and factor V Leiden mutations. The results of laboratory studies (borderline lupus anticoagulant, leukopenia, decreased platelet count, slightly elevated D-dimer concentration, and prolonged activated partial thromboplastin time) were suggestive of antiphospholipid syndrome or lupus; however, further biochemical tests excluded these causes. Performed again with an interval of 12 weeks, anti-cardiolipin antibodies in the IgG or IgM class, lupus anticoagulant and antibodies against β2-glycoprotein were negative. Moreover, IgM and IgG antibodies against CMV were detected. Transthoracic echocardiography and carotid artery ultrasonography were unremarkable. Treatment with glatiramer acetate was started 3 weeks after discontinuation of interferon beta-1a. After 2 weeks of glatiramer acetate therapy, we observed neurological worsening with fever, headache, impaired consciousness, left-sided weakness, and lower limb ataxia. Lumbar puncture revealed only a mild elevation of cerebrospinal fluid protein, no oligoclonal bands, and a negative encephalitis panel; meningitis was therefore ruled out. The brain MRI showed diffuse and limited hyperintense changes in fluid-attenuated inversion recovery (FLAIR) and T2 sequences located periventricularly in the subcortical white matter, mainly in the frontal and parietal lobes, in the pons, in the basal ganglia and in the corpus callosum. MRI revealed also post contrast leptomeningeal enhancement. Repeated FA showed new BRAOs and AWH in both eyes. Moreover, the patient reported hearing loss; however, pure tone audiometry was inconclusive because of the patient’s worsening condition. We also noted livedo reticularis and a maculopapular rash. SS was diagnosed based on these new findings. The diagnosis of MS was excluded, and glatiramer acetate therapy was discontinued. Treatment was started with Methylprednisolone (0.5–1.0 g) which was administered for 5 days; the total used dose was 3.0 g. Despite slight initial improvement, neurological deterioration occurred after 7 days when the steroids dose was reduced to 50 mg prednisone per day (a total used dose of 350 mg of prednisone). Neither plasma exchange (four courses) nor azathioprine improved the patient’s neurological condition. The patient’s neurological state improved only after use of a combination of corticosteroids, intravenous immunoglobulins, and azathioprine; visual acuity was 20/20 in both eyes, however in the fundus examination, BRAO’s in the peripheral retinal artery branches were still present in the right and left eye.