Susac’s syndrome as an autoimmune complication of alemtuzumab-associated immune reconstitution

Abstract

Susac’s syndrome is a rare autoimmune microangiopathy that affects the brain, retina and inner ear [1].It leads to the characteristic triad of encephalopathy, branch retinal artery occlusions (BRAOs) and vestibulocochlear involvement [2]. The encephalopathy is often characterised by headaches, which usually precede focal neurological signs [1]. BRAOs may be asymptomatic, or present with visual field deficits, blurred vision or photopsia [3].Vestibulocochlear involvement manifests as hearing loss, vertigo or tinnitus [3]. There have only been approximately 300 cases of Susac’s syndrome reported worldwide [2, 4]. We describe a case of Susac’s syndrome after alemtuzumab (Campath-1H) administration for solid organ transplantation. The onset of Susac’s syndrome after alemtuzumab treatment raises the possibility of it arising as an autoimmune complication of immune reconstitution. A 25-year-old woman with type 1 diabetes mellitus and end-stage diabetic nephropathy underwent a simultaneous kidney and pancreas transplant at Addenbrooke’s Hospital (Cambridge, UK). She received 30 mg subcutaneous alemtuzumab intraoperatively, and was commenced on 500 mg of mycophenolate mofetil (MMF) twice daily with tacrolimus. The MMF was reduced to 250 mg twice daily after 2 months in view of neutropenia. Fourteen months after her transplant, she presented to the emergency department with three days of bilateral intermittent tinnitus and positional vertigo, and one day of right-hand numbness, expressive aphasia and confusion. She did not experience any headaches. On examination, there was reduced sensation in the right arm, as well as right sided dysgraphaesthesia and sensory inattention. She had a low haemoglobin of 63 g/L (due to concurrent erosive gastritis), a normal white cell count, and a raised erythrocyte sedimentation rate of 28 mm. Anti-neutrophil cytoplasmic antibodies (ANCA) autoantibodies were negative. MRI of the brain showed multifocal, hyperintense lesions in the corpus callosum on fluid-attenuated inversion recovery (FLAIR) weighted sequences (Fig. 1), in keeping with ‘snowball’ lesions described as pathognomonic for Susac’s syndrome [5]. Cerebrospinal fluid (CSF) showed white cells 0.0/mm3, red cells 111/mm3, protein 0.23 g/L and glucose 3.4 mmol/L. CSF oligoclonal banding showed no evidence of intrathecal IgG synthesis, but similar oligoclonal IgG in both CSF and serum, suggesting a systemic inflammatory process. The absence of inflammatory changes within the CSF excluded cerebral vasculitis, and rendered acute disseminated encephalomyelitis (ADEM) unlikely, thus favoring a diagnosis of Susac’s syndrome. MRI spine was also normal, further reducing the likelihood of a diagnosis of multiple sclerosis, or ADEM. Audiology performed after resolution of her tinnitus was unremarkable (no sensorineural hearing loss). Ophthalmological examination revealed ischaemic retinopathy from diabetes, and a new retinal haemorrhage, but no evidence of BRAOs, Gass plaques, arteriolar wall hyperfluorescence or other retinal vasculitic changes. The ophthalmologists decided that the changes from ischaemic retinopathy were so extensive that they would obscure any changes due to Susac’s on a fluorescein angiogram, so it was not performed. After three days of IV methylprednisolone 1 g, her right arm numbness resolved and expressive dysphasia improved. She was discharged on 40 mg prednisolone daily, and MMF 500 mg twice daily. By 10 days after admission, she only had mild expressive dysphasia and a slight loss of dexterity in * Sarah J. Crisp [email protected]