Susac syndrome

Susac syndrome is characterized by the clinical triad of encephalopathy, hearing loss, and retinal artery branch occlusions, mostly in young women. To our knowledge, long-term outcome and impact of pregnancy have not been specifically addressed. We report a series of 9 patients (7 female, 2 male) followed at the same institution, with special emphasis on clinical outcome including pregnancy and long-term sequelae. Clinical, brain magnetic resonance imaging (MRI), funduscopy, retinal angiography, and audiogram data were recorded every 3-12 months. We also analyzed the 92 previously reported cases of Susac syndrome. Mean follow-up was 6.4 years. Age at onset was 30.4 years. The first symptom occurred between April and September in 7 of 9 patients in the current study, and in 68% of all patients. The complete triad at onset was clinically obvious in only 1 of 9 patients. Brain involvement was heralded by headache and symptoms of encephalopathy. Cerebrospinal fluid was abnormal in 5 patients showing pleocytosis (mean, 24.6; range, 6-85 cells/mL) and elevated protein level (mean, 210; range, 113-365 mg/dL). Over time, quantitative brain MRI analysis showed that the number of lesions diminished and did not parallel clinical flares, and MRI never normalized. At the end of follow-up, no patient had severe impairment, and all but 1 returned to work. Inner ear involvement was present at onset in 2 patients and occurred in others with a mean delay of 11 months. Initially unilateral in 3, it became bilateral in all. Mean hearing loss was 34 dB (range, 15-70 dB). Hearing loss never improved, either spontaneously or under treatment. The eye was involved at onset in 8 patients, and after 3 years in 1. All had multiple bilateral retinal artery branch occlusions and/or dye leakage with hyperfluorescence of the arterial wall on fluorescein angiography. Over time, angiography normalized in 3 patients. In others, it was still abnormal at the end of follow-up (range, 1.5-10 yr). On late findings, fluorescein leakage was more frequent than true arterial occlusion. Eye involvement was mostly asymptomatic, unilateral, peripheral, and resumed spontaneously to remit in other sites over time. Corticosteroids were efficient to treat encephalopathy, with relapses occurring when the dosage was tapered. Steroid treatment did not improve hearing loss or prevent new retinal arteriolar occlusions. Anticoagulation had a role in treating encephalopathy and retinal arteriolar occlusions. Three patients had 4 pregnancies. Two pregnancies needed induced abortion. One pregnancy was uneventful. One pregnancy was complicated with Susac disease flare in the early postpartum period. In conclusion, at the end of follow-up, most patients had returned to work and none had severe impairment. Pregnancy may affect the course of Susac syndrome, with relapse of encephalopathy postpartum. Our main finding was that the course of Susac syndrome is not self-limited as previously thought, since isolated retinal arteriolar involvement may occur as a very late manifestation.

Susac syndrome is an autoimmunological disease that is characterized by the clinical trial of encephalopathy, retinal artery occlusion and sensorineural hearing loss. Because of its rarity and similarities to other common disorders it is often misdiagnosed and therefore mistreated. Susac syndrome mainly affects patients at the age of 20–40 years and causes irreversible ischaemic changes which lead to disability and thus become a social problem. Only early diagnosis and prompt treatment is able to prevent them. We present a case of a 28-year-old Caucasian male who is an anabolic steroid abuser with temporal branch arterial occlusion in the left eye, auditory deficits, chronic headaches, ischaemic lesions in white and grey matter and corpus callosum in MRI, diagnosed as Susac syndrome and treated in the beginning with intravenously and orally administered steroids, followed by multiple treatment cycles of cyclophosphamide after periods of exacerbations. The administration of oral low doses of prednisolone stabilized the course of the disease. A multidisciplinary approach and establishment of treatment guidelines is required to accelerate the diagnosis and improve treatment effectiveness, thus ameliorating the prognosis and quality of life for patients suffering from Susac syndrome.

We report a case of a 19-year-old woman presenting bilateral neurosensorial hearing loss, mental abnormalities, and loss of visual field in the left eye. Visual acuity was 20/20 in OD and 20/25 in OS. Patient was examined systemically. Audiometry showed sensorineural hearing loss in both ears. The magnetic resonance imaging (MRI) of brain revealed multiple small lesions in the white matter in both cerebral hemispheres and at the corpus callosum. Fundoscopy showed bilateral normal optic disc and sheathing of the arterioles in the middle periphery of OD. Retinal edema and cotton-wool spots were observed. Fluorescein angiography showed bilateral peripheral occlusive arterial vasculopathy. The patient was diagnosed with Susac syndrome and treated with quetiapine fumarate, flunitrazepam, and prednisone, which resulted in stabile outcome. This case shows that a high index of suspicion leading to early recognition and treatment is important to avoid irreversible damage.

We present a 47-year-old woman with a 10-year disease course consisting of episodic confusion, aphasia, psychosis, depression, migrainous headaches and seizures. There was mild elevation of protein levels in the cerebrospinal fluid, progressive cerebral atrophy, and numerous small T1 hypointensities appearing as central "holes" in the corpus callosum on magnetic resonance imaging. She eventually expired due to status epilepticus and subsequent significant respiratory complications. In the central nervous system, there was generalized brain atrophy, and patchy labeling of blood vessels by antibodies to complement component 4d (C4d) and membrane attack complex. Innumerable small patches with loss of cell bodies (neurons and glial cells in gray matter and glial cells in white matter) and demyelination were scattered throughout the brain and spinal cord. There was no cavitation and the passing axons were mostly preserved. Large solid calcified foci were present predominantly in the pons along with disseminated focal calcification involving neuron cell bodies, neurites, and capillaries. Patchy labeling of glial cells and linear structures suggestive of myelin sheaths with C4d antibodies was observed while immunostains for SV40, tau, β-amyloid, alpha synuclein, p62, and trans-activation response DNA-binding protein 43 kDa were negative. Whole-exome sequencing did not reveal any clinically significant variants. Although the radiological findings are suggestive of Susac's syndrome (a rare condition characterized by encephalopathy, hearing loss, and branch retinal artery occlusion), in the absence of audiovisual manifestations, a definitive diagnosis cannot be rendered and therefore, this case may be representing a new entity. Further reports of similar cases are needed for clarification.

IntroductionWe report a case of Susac syndrome, initially suspected to be multiple sclerosis, and advocate diagnostic caution and high suspicion. We describe a successful therapeutic approach comprising corticosteroids, intra-venous immunoglobulin...

A 24-year-old woman developed encephalopathy, branch retinal artery occlusion, hearing loss, and had "snowball" lesions in the corpus callosum, classic findings of Susac syndrome (SuS). Despite intensive immunosuppressive therapy, she lapsed into a coma, and died 7 months after the onset of her illness. Neuropathological examination, revealed perivascular inflammation and vasculitis involving small vessels, associated with vascular narrowing and occlusion, and numerous microinfarcts diffusely throughout the brain. The findings establish SuS as a neuroinflammatory condition that can include vasculitis. This represents the most comprehensive report of the neuropathological findings in SuS.

Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis. In this multicenter cross-sectional observational study optical coherence tomography was performed in nine patients with a definite diagnosis of Susac syndrome. Data were compared with age-, sex-, and disease duration-matched relapsing remitting multiple sclerosis patients with and without a history of optic neuritis, and with healthy controls. Using generalised estimating equation models, Susac patients showed a significant reduction in either or both retinal nerve fibre layer thickness and total macular volume in comparison to both healthy controls and relapsing remitting multiple sclerosis patients. However, in contrast to the multiple sclerosis patients this reduction was not distributed over the entire scanning area but showed a distinct sectorial loss especially in the macular measurements. We therefore conclude that patients with Susac syndrome show distinct abnormalities in optical coherence tomography in comparison to multiple sclerosis patients. These findings recommend optical coherence tomography as a promising tool for differentiating Susac syndrome from MS.

Susac syndrome in a patient with chronic myelocytic leukemia: Consequence or coincidence?

Purpose Susac syndrome is a rare autoimmune microangiopathy that affects the precapillary arterioles of the brain, retina, and inner ear. It is typically characterized by a clinical triad of encephalopathy, branch retinal arteriolar occlusions (BRAOs), and sensorineural hearing loss. At present, reports of reperfusion of occluded retinal arterioles are scarcely reported in the literature. Methods Two case reports. Results Two pediatric patients presented with sudden visual field defects caused by multiple retinal arteriolar occlusions. Following appropriate immunosuppressive therapy, complete reperfusion of the occluded retinal arterioles was achieved. Conclusion These cases highlight the importance of the early recognition of Susac syndrome in children presenting with BRAOs, even in the absence of the complete triad. Retinal vascular occlusion in this condition may be reversible with timely and aggressive immunosuppression, underscoring the need for prompt diagnosis and consideration of biological agents for refractory pediatric diseases.

To characterize vestibulocochlear involvement in patients with Susac syndrome (SuS), a rare immune-mediated endotheliopathy of cerebral, retinal and inner ear microvasculature causing a triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss. The electronic patient files of 21 patients with SuS are reviewed for data on demography, clinical presentation, disease course and audiovestibular testing. All 21 patients experienced some form of audiovestibular complaints during the disease course, with vertigo and instability being most frequently reported, followed by hearing loss, tinnitus and aural fullness. These audiovestibular symptoms did not always coincide. Fifteen patients had objectified predominant low- to midfrequency sensorineural hearing loss and 8 out of 18 patients showed abnormalities on vestibular testing, most frequently vestibular evoked myogenic potential-abnormalities, indicating otolith dysfunction. Treatment protocols consisted of uniformly extensive immunosuppressive therapy and hearing loss remained mostly mild. Audiovestibular involvement is very common in patients with SuS. Characteristic findings include a "reverse-slope" configuration on audiological testing and otolith dysfunction on vestibular testing. Aggressive immunosuppression may prevent severe audiovestibular dysfunction. Symptoms as aural fullness and otolith dysfunction may indicate an underlying hydrops. Further investigations are necessary to elucidate the histopathological mechanisms underlying these preferentially involved cochleovestibular areas. Early recognition and treatment of SuS are important to stabilize or decrease disease activity and might also have beneficial effects on inner ear outcome. THE SUBMITTED MANUSCRIPT REPORTS DATA DERIVED FROM CLINICAL OBSERVATIONS IN HUMANS: Consent for the research was provided by the Ethics Committee of Ghent University hospital (application number 2019/1443, registration date 31/12/2021, principal investigator Guy Laureys).

BackgroundSusac syndrome (SuS) is a rare disorder thought to be caused by autoimmune-mediated occlusions of microvessels in the brain, retina and inner ear leading to central nervous system (CNS) dysfunction, visual disturbances due to branch retinal artery occlusions (BRAO), and hearing deficits. Recently, a role for anti-endothelial cell antibodies (AECA) in SuS has been proposed.ObjectivesTo report the clinical and paraclinical findings in the largest single series of patients so far and to investigate the frequency, titers, and clinical relevance of AECA in SuS.Patients and methodsA total of 107 serum samples from 20 patients with definite SuS, 5 with abortive forms of SuS (all with BRAO), and 70 controls were tested for AECA by immunohistochemistry employing primate brain tissue sections.ResultsIgG-AECA >1:100 were detected in 25% (5/20) of patients with definite SuS and in 4.3% (3/70) of the controls. Median titers were significantly higher in SuS (1:3200, range 1:100 to 1:17500) than in controls (1:100, range 1:10 to 1:320); IgG-AECA titers >1:320 were exclusively present in patients with SuS; three controls had very low titers (1:10). Follow-up samples (n = 4) from a seropositive SuS patient obtained over a period of 29 months remained positive at high titers. In all seropositive cases, AECA belonged to the complement-activating IgG1 subclass. All but one of the IgG-AECA-positive samples were positive also for IgA-AECA and 45% for IgM-AECA. SuS took a severe and relapsing course in most patients and was associated with bilateral visual and hearing impairment, a broad panel of neurological and neuropsychological symptoms, and brain atrophy in the majority of cases. Seropositive and seronegative patients did not differ with regard to any of the clinical or paraclinical parameters analyzed.ConclusionsSuS took a severe and protracted course in the present cohort, resulting in significant impairment. Our finding of high-titer IgG1 and IgM AECA in some patients suggest that humoral autoimmunity targeting the microvasculature may play a role in the pathogenesis of SuS, at least in a subset of patients. Further studies are warranted to define the exact target structures of AECA in SuS.

Susac syndrome is a vasculopathy affecting the central nervous system, retina and cochlea leading to the triad encephalopathy, branch retinal artery occlusions and hearing loss. To date, about 300 cases have been described in the literature. Three patients with confirmed Susac syndrome were evaluated for disease-specific retinal pathologies. In addition, the overall history of the disease is presented to put the ophthalmological pathology into context. All three cases showed a retinal occlusive microangiopathy with branch retinal artery occlusions. MRI imaging revealed snowball-like lesions of the corpus callosum in two of three cases. At the initial presentation not all criteria of the disease-specific triad encephalopathy, branch retinal artery occlusions, and hearing loss were fulfilled in the three patients. Interdisciplinary collaboration between neurologists, otorhinolaryngologists and ophthalmologists is mandatory to establish the diagnosis of the disease. The occurrence of the characteristic retinal pathology with small artery occlusions and a segmental vasculopathy should always lead to the differential diagnosis of Susac syndrome.

Susac syndrome: The importance of an early diagnosis.

The aim of this non-interventional study was to characterize retinal layer pathology in Susac syndrome (SuS), a disease with presumably autoimmune-mediated microvessel occlusions in the retina, brain, and inner ear, in comparison to the most important differential diagnosis multiple sclerosis (MS). Seventeen patients with SuS and 17 age- and sex-matched patients with relapsing-remitting MS (RRMS) and healthy controls (HC) were prospectively investigated by spectral-domain optical coherence tomography (OCT) including intraretinal layer segmentation in a multicenter study. Patients with SuS additionally received retinal fluorescein angiography (FA) and automated perimetry. Patchy thinning of the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer compared to corresponding sectors in RRMS and HC eyes (p < 0.003 for SuS vs RRMS and HC) was observed in 23/34 (68%) SuS eyes, particularly in temporal quadrants. The outer nuclear layer (ONL) and photoreceptor layers (PRL) were not affected. FA performed in 15/17 patients with SuS was negative for disease-specific branch retinal artery occlusions in all but 1 eye at the time of OCT examination and revealed no additional vascular abnormalities, even in severely damaged OCT areas. In a subset of patients with SuS, associations of visual field data with distinct retinal layers were observed. Distinct OCT patterns of scattered, scar-like intraretinal pathology in SuS eyes, sparing the ONL and PRL, suggest a retinal, but not choroidal, vascular pathomechanism and clearly differentiate SuS from RRMS. Depending on the disease stage, OCT and FA provide specific complementary diagnostic information in SuS.

Context: Susac Syndrome, was first described in 1979, by neurologist John Susac, and is characterized by a clinical triad consisting of: central nervous system dysfunction, visual changes and sensorineural hearing loss. Although the pathophysiology is not yet fully understood, the description occurs with microangiopathy involving arteries of the brain, retina and cochlea. The manifestation of the clinical triad has a monophasic and self-limiting course.This case report was approved by the Ethics Committee of Universidade Metropolitana de Santos. Case Report: The present case refers to a female patient, 40 years old, caucasian, and presented a sudden decrease in the visual acuity of the left eye, with visual blurring and dyschromatopsia. After 3 days, he sought medical assistance from an ophthalmologist, already presenting amaurosis of his left eye. Occlusion of distal branches of the retinal artery of the left eye was confirmed. He had a personal history of recurrent major depression and obsessive-compulsive disorder with sub-optimal response to drug treatment. Evaluated with neurology, referring to a decrease in asymmetric auditory acuity. Bilateral sensorineural hearing loss confirmed. Skull MRI was performed and showed multiple images of central lesions in the corpus callosum (“snow ball lesions”), as well as lesions in the white matter of the brain. Conclusions: The diagnosis of Susac syndrome was established and symptomatic treatment was performed, presenting with clinical stabilization.