Case Report of Spinal Cord Involvement in Susac Syndrome Masquerading as a Multiple Sclerosis Mimic

Abstract

We present a unique case of a 59-year-old woman with atypical Susac syndrome and prominent involvement of the spinal cord. She initially presented with progressive headaches, lower extremity weakness and hearing loss. Her MRI brain showed multiple enhancing lesions and her MRI spine showed a T8 enhancing lesion as well as a C2 cord infarct. She was treated with IV methylprednisolone with initial stabilization. However, she developed worsening encephalopathy and lower extremity weakness. Her repeat MRI brain showed new bilateral enhancing lesions and subacute infarcts. Given the increased burden of new lesions, she underwent a brain biopsy, which showed perivascular chronic inflammation within a small vessel distribution. Additionally, fluorescein angiography revealed bilateral branch retinal arterial occlusion (BRAO) and an audiogram demonstrated bilateral sensorineural hearing loss. She was diagnosed with Susac syndrome and treated with IV cyclophosphamide with improvement in her clinical exam. Spinal cord involvement is extremely rare for Susac syndrome, which commonly manifests as the classic triad of encephalopathy, BRAO and hearing loss. Her presentation with myelopathy highlights the importance of considering atypical presentations of well-established syndromes for optimal diagnosis and management.

Introduction

First described by John Susac in 1979, Susac syndrome classically presents with a triad of encephalopathy, branch retinal artery occlusion (BRAO) and hearing loss. ¹ The pathognomonic feature of Susac syndrome is snowball shaped infarcts of the corpus callosum. ² The postulated pathophysiologic mechanism is an autoimmune endotheliopathy affecting inter-hemispheric callosal, retinal and cochlear arteries, with some evidence to suggest a role of anti-endothelial cell antibodies. ³ Spinal cord involvement has rarely been described in Susac Syndrome. To our knowledge, there has been only one previous case report with a spinal cord lesion of undetermined significance described in the literature. ⁴ Herein, we report a patient with Susac’s syndrome and acute spinal involvement. Direct patient consent was obtained for permission to report her condition in this manuscript. The spinal cord infarct seen on diffusion sequences of MRI in our patient is a novel finding that has rarely been described in Susac Syndrome.

Case Presentation

A 59-year-old previously healthy woman presented with 6 weeks of persistent headaches, progressive lower extremity weakness and sensory loss. Within a month, she developed progressive encephalopathy and decreased hearing bilaterally. Neurological exam at presentation to a local hospital revealed lower extremity weakness in a myelopathic pattern, hyperreflexia and a T8 spinal sensory level. MRI brain with contrast revealed T2 hyperintense lesions, of which most were also contrast enhancing on the T1-post contrast sequence, involving the corpus callosum, bilateral periventricular and subcortical white matter. Some lesions also demonstrated diffusion restriction (Figures 1A,B,E). MRI spine showed a C2 spinal cord lesion with DWI restriction, possible ADC correlate, without T2 hyperintensity and patchy T1-post contrast enhancement concerning for possible spinal cord infarct vs acute demyelinating lesion (Figure 1C with representative DWI sequence). There was also a T2 hyperintense, non-contrast enhancing intramedullary left T8 lateral spinal cord lesion (Figure 1D). Cerebrospinal fluid (CSF) analysis showed 9 nucleated cells (reference range <5cells/µL) with lymphocytic predominance, elevated CSF glucose (78 mg/dl, normal range 40-70 mg/dl), elevated CSF protein (61 mg/dl, normal range 15-45), elevated CSF IgG index (4.9, normal <3.4) and no oligoclonal bands. Serum and CSF autoimmune encephalopathy panel, serum anti-aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies in serum and CSF were negative. There was no evidence of a hypercoagulability disorder or systemic inflammatory process found on diagnostic studies.

Figure 1.

MRI brain showing sagittal (A) and axial (B) T2 FLAIR images demonstrating cotton-ball lesions in the corpus callosum, with associated diffusion restriction (E). MRI Spine with DWI sequence (C) showing diffusion restricting lesion in the cervical spinal cord at C2 level. MRI thoracic spine with T2/STIR sequence (D) showing hyperintense lesion at T8 level. Fluorescein angiogram (F) showing retinal arterial contrast leakage suggestive of vasculitis.

Treatment with IV methylprednisolone 1 gm/day for 5 days was initiated for a presumed diagnosis of demyelinating disease given enhancing brain and spinal cord lesions. As lesions in the corpus callosum increased, plasma exchange was initiated followed by rituximab for presumed fulminant multiple sclerosis. However, due to an anaphylactic reaction, rituximab was discontinued. She was discharged to rehab where her motor deficits remained stable although the headaches and encephalopathy progressed prompting admission to our institution a few weeks later.

Her pertinent neurological exam, approximately 6 weeks after initial presentation, was notable for encephalopathy, proximal upper & lower extremity weakness in a myelopathic pattern with spasticity and diffuse hyperreflexia in the arms and legs, sensory level below C2, sustained ankle clonus, bilateral Babinski signs and reduced hearing bilaterally. Repeat MRI brain demonstrated increased number of DWI restricting subcortical and periventricular white matter lesions with predilection for the corpus callosum. Several of these lesions showed diffusion restriction suggestive of subacute infarcts in a small vessel distribution. Brain biopsy revealed perivascular chronic inflammatory changes and fibrinoid vessel wall changes in a small vessel distribution suggestive of an inflammatory microangiopathy as seen in Susac Syndrome.

A fluorescein angiogram showed bilateral occlusive branch retinal arterial vasculitis despite absence of appreciated visual symptoms (Figure 1F). An audiogram showed sensorineural hearing impairment at 6000 Hz. Her constellation of symptoms, presence of multifocal T2 lesions with predilection for the corpus callosum with a “snowball” appearance, occlusive retinal vasculitis, sensorineural hearing impairment, and perivascular microangiopathy on brain biopsy led to a diagnosis of Susac Syndrome with atypical spinal cord involvement, rather than primary CNS vasculitis which is transmural. ⁵ She was treated with IV methylprednisolone 1 gm/day for 5 days followed by a prolonged steroid taper, IV cyclophosphamide 750 mg/m² monthly for 6 months and oral mycophenolate as steroid sparing therapy.

At 1 year, she remains clinically stable on mycophenolate without development of new lesions on serial imaging, and with improved fluorescein angiogram findings and noticeable improvement in her encephalopathy. She remains appreciative of her care and grateful for her clinical improvement and stability on oral mycophenolate.

Discussion

Susac syndrome is an autoimmune endotheliopathy that is best recognized when the classic triad of encephalopathy, branch retinal artery occlusion and hearing loss are collectively present. ¹ However, the classic triad may be rare and 1 review reports only 13% of patients had all features of the classic triad. ⁶ In the absence of recognition of all 3 features the diagnosis may be initially elusive, particularly in the acute inpatient setting when patients may present with significant encephalopathy and resultant limited ability to report symptoms such as visual or hearing loss. Although classic “snowball” or “cannon-ball” white matter lesions seen on sagittal MRI brain FLAIR sequences may further lead towards the diagnosis, it is important to acknowledge that other less common imaging features may also be present and should not negate appropriate immunotherapy initiation while a conclusive diagnosis is pursued. A radiographic differential diagnosis considered for patients with neurologic deficits and corpus callosal FLAIR lesions includes demyelinating diseases, such as multiple sclerosis, among other inflammatory processes such as vasculitides and inflammatory endotheliopathy as occurs in Susac disease. Furthermore, infarcts involving the corpus callosum could create a similar pattern. Oligoclonal bands are relatively uncommon in Susac disease with 1 study reporting oligoclonal bands in up to 42% of Susac patients as compared to 98% of patients with multiple sclerosis. ⁶ Spinal lesions, are rare in Susac disease, thus prompting the report of this case. Our patient’s paracentral spinal cord lesion was within an arterial territory supplied by sulco-commissural branches of the anterior spinal artery. ⁷ These are smaller endothelial branches congruent with the distribution thought to be most affected by endotheliopathy in the corpus callosum in Susac syndrome.^2,8 Therefore, we postulate that by virtue of its pathophysiological mechanism affecting endothelial vessels, spinal cord involvement can also occur. The occurrence of myelopathy, while distinctly rare, is within the pathophysiologic spectrum of Susac disease and should not distract from this diagnosis where appropriate. Further studies are needed to characterize spinal cord infarctions in Susac syndrome.

ORCID iD

Giovanna S. Manzano https://orcid.org/0000-0002-9991-9222