Susac's Syndrome

Overview of a case of Susac Syndrome.

Indiana University School of Medicine Susac Syndrome David O. Sohutskay1, Kevin E. Lai, MD2,Linda S. Williams, MD2,3, Devin D. Mackay, MD3,4,5 1Indiana University School of Medicine, 2Indianapolis VA Roudebush Medical Center, University Department of Neurology, 4Indiana University Department of Ophthalmology 5Indiana University Department of Neurosurgery 3Indiana INDIANA UNIVERSITY SCHOOL OF MEDICINE History • At time of initial visit in August 2017, patient was a 46-yearold male with past medical history of vitiligo • He first noticed hearing loss and tinnitus in 1999 requiring hearing aids, and noticed paroxysmal episodes of hearing loss, tinnitus and vertigo that lasted minutes to hours On audiometry later in the disease course (2020) he was found to have sensorineural hearing loss throughout the tested 2508000 Hz range, more prominent at higher frequencies. INDIANA UNIVERSITY SCHOOL OF MEDICINE Vision Loss • At initial visit in August 2017 patient was referred for vision loss in the left eye • He had previously developed a right eye inferior visual field defect in 2015 and diagnosed with a branch retinal artery occlusion Table: Results of vision examination at initial presentation Test Right Eye Left Eye Visual Acuity 20/20+1 20/25 Color Vision 14/14 Plates 14/14 Plates Relative Afferent Pupillary Defect None None Amsler Grids Full Full INDIANA UNIVERSITY SCHOOL OF MEDICINE Vision Loss • In subsequent years the vision loss improved and stabilized August 2017 Humphrey visual fields (24-2 SITA-Fast) at the initial visit in 2017 showed an inferonasal step in the right eye and mostly inferior depression in the left eye Right Eye Mean deviation of –6.06 db Mean deviation of –8.93 db Mean deviation of –4.79 db Mean deviation of –7.02 db March 2022 • Left Eye INDIANA UNIVERSITY SCHOOL OF MEDICINE Fundus Photography • Fundus imaging August 2017 showed mid-arteriolar (Gass) plaques in the left eye superiorly and inferiorly, and a small plaque in the right eye inferiorly • A retinal nerve fiber layer hemorrhage (flame hemorrhage) and retinal nerve fiber layer infarcts (cotton wool spots) in the left eye at the site of a new branch retinal artery occlusion • The right eye did not show active occlusion or hemorrhage Right Eye Left Eye INDIANA UNIVERSITY SCHOOL OF MEDICINE Fluorescein Angiography Right Eye At a follow up visit in October 2018, angiography of the right eye showed normal transit with no capillary drop or leakage Left Eye Angiography of the left eye showed normal transit, capillary dropout (black arrow) distal to the site of a superonasal branch retinal artery occlusion with focal leakage (red arrow) INDIANA UNIVERSITY SCHOOL OF MEDICINE Optic Nerve and Ganglion Cell Analysis • OCT of the optic nerve at the initial visit showed thinning in the right eye, and thickening due to nerve fiber layer edema at the site of the cotton wool spot seen on fundoscopy • Ganglion cell thinning was present in both eyes Right Eye Left Eye Right Eye OCT in August 2017 showed an average retinal nerve fiber layer thickness of 83 microns in the right eye and 128 microns in the left eye Left Eye The ganglion cell analysis showed superotemporal thinning in the right eye and very mild superonasal thinning in the left eye INDIANA UNIVERSITY SCHOOL OF MEDICINE Optic Nerve Atrophy • Over time the patient developed optic nerve fiber layer thinning in both eyes due to the prior branch retinal artery occlusions OCT in May 2020 showed an average retinal nerve fiber layer thickness of 87 microns in the right eye and 79 microns in the left eye INDIANA UNIVERSITY SCHOOL OF MEDICINE Cognition and Neuroimaging • The patient's cognitive symptoms included migraine headaches, slowed thinking, and fatigue MRI of the brain in 2018 was unremarkable except for small white matter hyperintensities predominantly in the right frontal lobe No lesions were seen in the deep white matter or corpus collosum INDIANA UNIVERSITY SCHOOL OF MEDICINE Final Diagnosis • Susac syndrome is a rare microvascular endothelial disease with a classic triad of branch retinal artery occlusions, sensorineural hearing loss, and subacute encephalopathy • Many patients do not have the complete triad – Some cases can be categorized as having predominantly encephalopathy or predominantly branch retinal artery occlusions and hearing loss – In encephalopathic patients, classic MRI findings include circular lesions in the corpus collosum, as well as deep grey matter and posterior fossa involvement • In Susac syndrome, the corpus callosum involvement seen on MRI is central, sparing the interface with the ventricle, unlike in demyelinating disease • Anti-endothelial antibodies are found in some patients, and cytotoxic CD8+ T cells may play a pathologic role • Long-term immunosuppression with steroids and other agents is generally required INDIANA UNIVERSITY SCHOOL OF MEDICINE Treatment and Outcome • The patient was initially treated with 1g methylprednisolone q3d, monthly IVIG, and mycophenolate 1g BID • However, he continued to experience vision and hearing loss so oral prednisone 60mg q30d was added followed by a taper, and monthly cyclophosphamide pulses • The acute symptoms resolved, and the patient was transitioned to mycophenolate monotherapy • He experienced several relapses between 2017 and 2020 requiring additional IVIG and cyclophosphamide • In 2021 the patient was transitioned to rituximab and methotrexate, following which he had two additional episodes of vision and hearing loss, and has been stable since INDIANA UNIVERSITY SCHOOL OF MEDICINE Treatment and Outcome • Follow up fundoscopy in 2022 shows resolution of acute occlusion, hemorrhage and cotton wool spots, though a plaque remained present in the right eye • Despite recurrence of visual/auditory symptoms, multiple brain MRI from 2019-2021 have also been unremarkable Right Eye Left Eye INDIANA UNIVERSITY SCHOOL OF MEDICINE Differential Diagnosis • Differential diagnosis for Susac syndrome includes autoimmune and inflammatory disease, vasculitis, and causes of vision and hearing loss such as: – – – – – – – – Multiple Sclerosis Acute Demyelinating Encephalomyelitis Primary Angiitis of the Central Nervous System Behcet Disease Systemic Lupus Erythematosus Vogt-Koyanagi-Harada Disease Cogan Disease Eales Disease INDIANA UNIVERSITY SCHOOL OF MEDICINE References 1. Dörr J, Krautwald S, Wildemann B, Jarius S, Ringelstein M, Duning T, Aktas O, Ringelstein EB, Paul F, Kleffner I. Characteristics of Susac syndrome: a review of all reported cases. Nature Reviews Neurology. 2013 Jun;9(6):307-16. 2. Kleffner I, Dörr J, Ringelstein M, Gross CC, Böckenfeld Y, Schwindt W, Sundermann B, Lohmann H, Wersching H, Promesberger J, von Königsmarck N. Diagnostic criteria for Susac syndrome. Journal of Neurology, Neurosurgery & Psychiatry. 2016 Dec 1;87(12):1287-95. 3. Rennebohm RM, Asdaghi N, Srivastava S, Gertner E. Guidelines for treatment of Susac syndrome–An update. International Journal of Stroke. 2020 Jul;15(5):484-94. 4. Egan RA. Diagnostic criteria and treatment algorithm for Susac syndrome. Journal of Neuro-Ophthalmology. 2019 Mar 1;39(1):60-7. 5. García-Carrasco M, Mendoza-Pinto C, Cervera R. Diagnosis and classification of Susac syndrome. Autoimmunity reviews. 2014 Apr 1;13(4-5):347-50. 6. Vishnevskia-Dai V, Chapman J, Sheinfeld R, Sharon T, Huna-Baron R, Manor RS, Shoenfeld Y, Zloto O. Susac syndrome: clinical characteristics, clinical classification, and long-term prognosis. Medicine. 2016 Oct;95(43). 7. Gross CC, Meyer C, Bhatia U, Yshii L, Kleffner I, Bauer J, Tröscher AR, Schulte-Mecklenbeck A, Herich S, Schneider-Hohendorf T, Plate H. CD8+ T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome. Nature communications. 2019 Dec 18;10(1):1-9. INDIANA UNIVERSITY SCHOOL OF MEDICINE