Radiologically Isolated Syndrome: Pathologically Defined as Demyelinating Disease (P1.391)

Objective: Describe three patients where pathological examination confirmed central nervous system (CNS) inflammatory demyelinating disease as the etiology of radiologically isolated syndrome (RIS). Background: RIS is the discovery of MRI lesions highly typical of CNS demyelinating disease prior to clinical symptom onset. While RIS often leads to definite multiple sclerosis (MS), the observed asymptomatic MRI lesions lack pathological confirmation. Methods: Three patients were evaluated at RIS consortium centers. Clinical and radiological evaluations and prospective follow-up were performed. Presentations leading to imaging were: intractable upper extremity pain, pituitary investigation for hormonal imbalance, and control volunteer for MRI study. Brain MRI showed a large, gadolinium-enhancing lesion with additional non-enhancing white matter lesions. Diagnostic brain biopsy was performed in all to exclude primary CNS neoplasm. Five µm formalin-fixed paraffin-embedded sections were stained for hematoxylin/eosin, Luxol fast blue, periodic acid Schiff and Bielschowsky’s silver. Immunohistochemistry was performed with avidin-biotin-complex method for CD68, neurofilaments, glial fibrillary acidic protein, and myelin proteolipid protein. Results: The patients’ mean age at initial MRI and biopsy was 36 years (range 29-43) 2 were women and mean follow up duration was 9.5 years. Pathology confirmed inflammatory demyelinating disease compatible with MS in all three cases. White matter lesions were characterized by active demyelination with myelin-laden macrophages, relative axonal preservation, and reactive gliosis, including Creutzfeldt-Peters cells. Spinal cord MRI was available in one patient at presentation and was normal. Cerebrospinal fluid showed elevated oligoclonal bands in one of two tested. One patient was diagnosed with relapsing remitting MS 15 months following initial MRI and initiated disease modifying therapy (DMT). Two patients evolved radiologically one year following presentation remaining RIS without attacks or progressive impairment; one initiated, then discontinued, DMT and the other has not initiated DMT. Conclusions: The pathology of RIS is indistinguishable from classic MS pathology. Disclosure: Dr. Keegan has received research support from Terumo BCT. Dr. Guo has nothing to disclose. Dr. Okuda has received personal compensation for activities with Acorda Therapeutics, Genzyme, Novartis, and TEVA Neuroscience as a speaker, consultant, or advisory board member. Dr. Okuda has received research support from Biogen Idec. Dr. Siva has received personal compensation for activities with Biogen Idec. Dr. Pelletier has received personal compensation for activities with CNS Imaging Consultant, LLC as a consultant. Dr. Kantarci has nothing to disclose. Dr. Lucchinetti stands to receive royalty payments for commercial assays. Dr. Lebrun Frenay has nothing to disclose.