Susac Syndrome TESTING

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Title: Susac Syndrome
Author (s): Wilkinson, Samuel, MD; Nydegger, Jacob; Jebaraj, Abigail, MD; Seay, Meagan, DO
Photographer: Olga Sessions
Date: 07/26/21
Keywords/Main Subjects: Susac syndrome; branch retinal artery occlusion; retina
Diagnosis: Susac syndrome

Description of Case:

A 43-year-old female presented to the emergency department (ED) after an abnormal MRI at an outside hospital.

Six weeks prior to presentation, she developed an acute onset of nausea, vomiting, and headaches more severe than her typical migraine headache. Additionally, she began experiencing episodic confusion. Two weeks prior, she developed hearing loss with a whooshing tinnitus in her left ear. One day prior to presentation, she underwent an audiometry testing significant for decreased hearing in her left ear compared to right. Given her constellation of symptoms, an MRI brain was done which showed innumerable punctate T2/FLAIR hyperintensities throughout the parenchyma of the bilateral cerebral and cerebellar hemispheres with prominence within the corpus callosum, consistent with small vessel vasculitis (Figure 1, Figure 2). She was urgently directed to the emergency department.

Wilkinson, Nydegger, Jebaraj, Seay- Susac Figure 1

Figure 1: Sagittal T2 FLAIR MRI image demonstrating characteristic hyperintense lesions in the corpus callosum

Wilkinson, Nydegger, Jebaraj, Seay- Susac Figure 2

Figure 2: Axial T2 FLAIR MRI image demonstrating hyperintense lesions in the corpus callosum

Her past medical history included depression and migraine with vertigo and visual aura well-managed with rizatriptan. Her past surgical history was significant for remote spine and hip surgeries. Her social and family histories were non-contributory.

The patient was afebrile and hemodynamically stable on presentation. Neurologic examination revealed hyperreflexia of the left upper and lower extremities. She was oriented to person and place only and had difficulty with simple math. Her language function was intact without dysarthria. Cranial nerve function was intact other than hearing deficits.

Laboratory results were notable for elevated C-Reactive Protein (4.7 mg/dL) and sedimentation rate (32 mm/hr). Her cerebrospinal fluid (CSF) was remarkable for elevated white blood cells (26 /uL) and elevated protein (295 mg/dL). She had no oligoclonal bands. Additionally, her antinuclear antibody (ANA) was positive (speckled pattern, 1:160). Further workup was negative for , VZV antibody, Hepatitis C, Cryoglobulin, ANCA, anti-dsDNA, HIV, Smith antibody, SSA, SSB, Scl-70, Jo-1, VDRL, Quantiferon TB Gold Plus, and Hepatitis B.

The patient was admitted for management and further workup of small vessel vasculitis. She was started on acyclovir for possible viral meningitis. Given her history, MRI imaging, and lab testing, the suspected diagnosis was Susac syndrome.

On Day 2, she was started on intravenous methylprednisolone. Ophthalmology was consulted for an examination. Her examination was remarkable for visual acuity of 20/25 OD (right eye) and 20/25 OS (left eye). Her visual fields were full to confrontation OU (both eyes), her color vision was normal with Ishihara color plates OU, and she had no afferent pupillary defect OU. Her extraocular movements were full. Her intraocular pressures were 21 OD and 19 OS. Dilated fundus examination was unremarkable, however, a peripheral view was difficult due to patient confusion and inability to participate in examination.

On Day 4, fluorescein angiography (FA) was performed and revealed a normal arm to retina time with multiple bilateral branch retinal artery occlusions, right mild periphlebitis temporally, and left segmental arteriolitis of the main arcades (Figure 3 and Figure 4).

Wilkinson, Nydegger, Jebaraj, Seay- Susac Figure 3

Figure 3: Fluorescein angiogram of the right eye demonstrating multiple branch retinal artery occlusions (yellow arrows) characterized by arteriolar vascular filling defects and mild periphlebitis temporally

Wilkinson, Nydegger, Jebaraj, Seay- Susac Figure 4

Figure 4: Fluorescein angiogram of the left eye demonstrating multiple branch retinal artery occlusions characterized by arteriolar vascular filling defects (yellow arrows) and vessel leakage (blue arrows) consistent with segmental arteriolitis of the main arcades

On Day 5, she began treatment with intravenous immunoglobulin (IVIG) 2 grams per kilogram divided over 2 days.

During her hospitalization, her Montreal Cognitive Assessment (MoCA) testing improved from 11 out of 30 (Day 2) to 23 out of 30 (Day 6).

She was discharged home on Day 6 of hospitalization with outpatient treatment plan of IVIG infusion 1 g/kg every 2 weeks, mycophenolate mofetil 500 mg twice daily, and prednisone 60 mg daily.

At the one month follow up, she reported improved mental status but persisting decreased hearing in her left ear. A repeat FA showed multiple BRAOs bilaterally, mild periphlebitis in the right eye, and resolved arteriolitis of the main arcades in the left eye with some mild leakage versus staining in the nasal macula. Overall, she had an improved FA without any new occlusions.

Epidemiology:

Susac syndrome is characterized as a rare autoimmune disease affecting small blood vessels in the brain, inner ear, and retina. The most common symptoms of this disease are encephalopathy, hearing loss, and vision loss.1 Susac syndrome, although rare, has been shown to be more common in females having a 3:1 female to male ratio.2 Relapses of the condition have been noted around the same time as pregnancies in women, which may contribute to the increased female to male ratio.2 While not limited to this age group, the majority of diagnosed individuals fall between the ages of 20 and 40.3

Genetics:

Evidence has not been found to show that this is an inherited condition and there have been no documented familial cases.3

Signs and Symptoms:

Characteristic findings in Susac syndrome are encephalopathy from central nervous system dysfunction, vision changes, and sensorineural hearing loss. Symptoms affecting the central nervous system include memory loss, cognitive deficits, seizures, psychiatric disturbances, cranial nerve dysfunction, sensory loss, motor loss, aphasia, and headaches. Headaches are the most common and often present before the other symptoms by up to 6 months. Visual symptoms include vision loss due to branch retinal artery occlusions (BRAO). Such occlusions can present themselves as altitudinal visual field defects or scintillating scotomas. Also, blurred vision and photopsias have been reported. Most characteristically, patients will have multiple, recurrent BRAO without signs of intraocular inflammation.4 Hearing loss can be bilateral or unilateral, and typically affects low- and mid-frequencies on audiometry.5 While many of these symptoms can be reversed, hearing loss in Susac syndrome is largely irreversible-sometimes requiring cochlear implants.6 Notably, not all symptoms may present themselves in every case.2

Imaging:

Magnetic resonance imaging (MRI) is the preferred method for neuroimaging of suspected cases of Susac syndrome. MRI of the brain will be remarkable for punched-out lesions in the corpus callosum.7 Fluorescein angiography (FA) is used to best visualize and confirm ophthalmic examination findings of BRAO. FA should be repeated at a later date if it is not initially seen due to likelihood of occurrence.

Treatment:

The escalation of therapy depends upon the type and severity of associated symptoms. Some cases respond well to treatment while others recur after two years and, on rare occasion, develop a chronic course. A glucocorticoid—typically high dose methylprednisolone—is considered first line treatment. Approximately 10% of patients will respond to initial glucocorticoid treatment.7 Cyclophosphamide, plasmapheresis, and IVIG are considerations for severe or persistent cases. Anticoagulation and aspirin are therapeutic adjuncts as well. Other immunosuppressive treatments, such as azathioprine and tacrolimus, can be used after the acute phase of the disease. Additionally, anticoagulation can be initiated. More aggressive treatment is required for severe cases involving the central nervous system.8

Prognosis:

The majority of patients respond well to treatment. 54% of cases resolve within two years, while 42% of cases recur beyond two years, and 4% become chronic.2 In rare cases, Susac syndrome can be fatal.9 Common chronic symptoms include hearing loss, gait disturbance, and cognitive deficits. Given the rarity of the condition, prognosis is thought to depend upon severity of disease at presentation. Immediate treatment is indicated if there is suspicion of Susac syndrome to prevent morbidity and mortality.7

Summary of the Case:

This is a case of a 43-year-old female with Susac syndrome who presented with progressively worsening encephalopathy and hearing loss who was found to have bilateral, multiple branch retinal artery occlusions on fluorescein angiography and MRI T2/FLAIR hyperintense lesions throughout her brain, particularly the corpus callosum.

References:

  1. Saux A, Niango G, Charif M, et al. Susac’s syndrome, a rare, potentially severe or lethal neurological disease. J Neurol Sci. 2010;297(1-2):71-73. doi:10.1016/j.jns.2010.07.020
  2. Dörr J, Krautwald S, Wildemann B, et al. Characteristics of Susac syndrome: A review of all reported cases. Nat Rev Neurol. 2013;9(6):307-316. doi:10.1038/nrneurol.2013.82
  3. Susac syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Accessed June 15, 2021. https://rarediseases.info.nih.gov/diseases/7713/disease#ref_13094
  4. Sauma J, Rivera D, Wu A, et al. Susac’s syndrome: an update. Br J Ophthalmol. 2020;104(9):1190-1195. doi:10.1136/BJOPHTHALMOL-2019-315597
  5. Vishnevskia-Dai V, Chapman J, Sheinfeld R, et al. Susac syndrome: clinical characteristics, clinical classification, and long-term prognosis. Medicine (Baltimore). 2016;95(43). doi:10.1097/MD.0000000000005223
  6. Roeser MM, Driscoll CLW, Shallop JK, Gifford RH, Kasperbauer JL, Gluth MB. Susac syndrome – A report of cochlear implantation and review of otologic manifestations in twenty-three patients. Otol Neurotol. 2009;30(1):34-40. doi:10.1097/MAO.0B013E31818B6AC2
  7. B G-G, M P, E C. Susac syndrome–clinical insight and strategies of therapy. Eur Rev Med Pharmacol Sci. 2015;19(9):1729-1735. Accessed July 7, 2021. https://pubmed.ncbi.nlm.nih.gov/26004617/
  8. Susac Syndrome – EyeWiki. Accessed June 16, 2021. https://eyewiki.org/Susac_Syndrome#cite_ref-greco2_2-0
  9. Agamanolis DP, Klonk C, Bigley K, Rennebohm RM. Neuropathological Findings in Susac Syndrome: An Autopsy Report. J Neuropathol Exp Neurol. 2019;78(6):515-519. doi:10.1093/JNEN/NLZ031

Faculty Approval: Meagan Seay, DO

Copyright statement: Samuel Wilkinson, MD; Jacob Nydegger; Abigail Jebaraj, MD; Meagan Seay, DO ©2021. For further information regarding the rights to this collection, please visit: http://morancore.utah.edu/terms-of-use/