Therapeutic plasma exchange in refractory Susac's syndrome: A brief report

Susac's syndrome (SuS) is an autoimmune endotheliopathy that typically presents with the clinical triad of encephalopathy, hearing loss, and branch retinal artery occlusion. It has a wide range of possible presentations, and its pathogenesis remains uncertain. Fulminant and refractory cases are difficult to treat, and no standard treatment protocol has been established. However, therapeutic plasma exchange (TPE) has been described as an adjunctive therapy in several SuS cases. Herein we present a case of a 63‐year‐old male with debilitating encephalopathy and recent hearing and vision loss, who responded favorably to TPE. Given this and other published reports of plasma exchange therapy for SuS, treatment protocols should consider TPE in early stages of disease.


| INTRODUCTION
Susac's syndrome (SuS), is a rare endotheliopathy 1 with an estimated prevalence of 400 cases worldwide, which may be under-representative due to the difficulty of diagnosis. 2,3SuS is frequently characterized by the clinical triad of encephalopathy, hearing loss, and branch retinal artery occlusion (BRAO), that most commonly presents in women in the third and fourth decade of life. 1,2Presentation is variable, making diagnosis difficult. 2Symptoms have classically been attributed to inflammatory mediators or autoantibodies such as anti-endothelial cell IgG1 antibodies (AECA) 4,5 ; however, recent data from Gross et al. demonstrated a possible role in disease pathogenesis by CD8+ cytotoxic T-cells. 3 A typical workup includes CNS imaging, to visualize the typical callosal features, 6,7 angiography of the retina for assessment of BRAOs, and vestibulocochlear testing.These classic radiologic features may or may not be present. 8Reported treatments include immune-modulating therapies such as corticosteroids, IVIG, cyclophosphamide, and rituximab. 5,6In fulminant or refractory cases, therapeutic plasma exchange (TPE) may be considered as adjunctive therapy, 7,9 though no agreed-upon treatment protocol exists. 7This disease is typically self-limited, but early diagnosis and treatment may prevent blindness, deafness, and major cognitive disorder. 7

| CASE
A 63-year-old male presented to the emergency department in early 2023, bed-ridden and minimally responsive, 6 days after a seizure.At baseline, he is fully oriented, alert, interactive, and ambulatory with a cane.He has a history of suspected prior Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in 2013, treated with TPE and IVIG, and subsequent recurrent focal seizures with impaired consciousness.Prior 14-3-3 protein testing results were indeterminate and non-supportive of a Creutzfeldt-Jakob diagnosis.Additionally, his wife reports he has had progressive vision and hearing loss over the past 4 to 5 months.
At admission, he was arousable to touch but nonverbal.Once admitted, he was found to have fluctuating orientation and alertness, and waxing and waning left-sided hemiparalysis.Initial treatment consisted of corticosteroids, antiepileptics, and antibiotics to address potential infectious etiologies.CT and MRI assessments of his head showed no acute abnormalities and no callosal lesions, and anti-NMDA-R antibody testing was negative.A continuous EEG showed mild background slowing without epileptiform activity.Given the minimal response to medical therapies and history of encephalopathy responsive to plasma exchange, TPE was initiated.

| METHODS
IRB approval was not required for this report.The estimated plasma volume was 3300 mL.A single volume TPE was performed on a TerumoBCT (Lakewood, Colorado), Spectra Optia, V12.0.3 through a central venous catheter.Single-volume TPE was performed daily for five consecutive days using 5% albumin as the sole replacement fluid on days one and two.On days three through five, 5% albumin with 500 mL of fresh frozen plasma was used to complete the single-volume exchange to maintain coagulation parameters.ACD-A was used as the anticoagulant.

| RESULTS
Following the second TPE, the patient was responsive to name but had difficulty remaining alert.Following the fourth treatment, he woke spontaneously and was able to follow simple commands and answer simple questions.He became oriented to self, place, and month.Following the final treatment, he was nearing his baseline function, only with fatigue and inability to remember the previous week.

| DISCUSSION
TPE may be an effective method for the treatment of SuS.There are no recommendations included in the 9th Special Issue of the ASFA guidelines for treatment of SuS. 10 In a retrospective study of nine patients who underwent TPE for SuS, eight of nine patients showed symptomatic improvement or disease stabilization, with the last patient lost to follow-up. 9Plasma exchanges are an effective means of removing inflammatory mediators and both IgM and IgG autoantibodies.Although once a promising marker of disease, AECAs have now been characterized in several systemic autoinflammatory conditions making specificity questionably reliable. 4,5Cytotoxic Tcells, which are not removed in TPE, may also contribute to pathogenesis, in concert with soluble mediators.This mutlifactorial etiology does not preclude the use of TPE in disease modification.

| CONCLUSION
SuS is a rare autoimmune disease with potentially devastating outcomes and few reliable treatment options.TPE should be considered for treatment to control and prevent symptom progression.More research and reports are needed to fully understand its long-term efficacy.