Susac Syndrome Research Articles

Diagnosis, differential diagnosis and misdiagnosis of Susac syndrome.

Background and purposeSusac syndrome (SuS) is an inflammatory condition of the brain, eye and ear. Diagnosis can be challenging, and misdiagnosis is common.MethodsThis is a retrospective review of the medical records of 32 adult patients from an Australasian cohort of SuS patients.ResultsAn alternative diagnosis prior to SuS was made in 30 patients (94%) with seven patients receiving two or more diagnoses. The median time to diagnosis of SuS was 3 months (range 0.5–100 months). The commonest misdiagnoses were migraine in 10 patients (31%), cerebral vasculitis in six (19%), multiple sclerosis in five (16%) and stroke in five (16%). Twenty‐two patients were treated for alternative diagnoses, 10 of whom had further clinical manifestations prior to SuS diagnosis. At presentation seven patients (22%) met criteria for definite SuS, 19 (59%) for probable SuS and six (19%) for possible SuS. Six patients (19%) presented with brain–eye–ear involvement, 14 with brain–ear (44%), six with brain–eye (19%) and six (19%) with only brain involvement. In patients with the complete triad of symptoms the median delay to diagnosis was 3 months (range 1–9 months) compared to 5.25 months (range 0.5–100 months) for patients with encephalopathy and ocular symptoms at presentation.ConclusionsSusac syndrome patients are frequently misdiagnosed at initial presentation, despite many having symptoms or radiological features that are red flags for the diagnosis. Delayed diagnosis can lead to patient morbidity. The varied ways in which SuS can present, and clinician failure to consider or recognize SuS, appear to be the main factors leading to misdiagnosis.

Susac Syndrome: an uncommon cause of impaired vision

A 35-year-old Caucasian woman presented an abrupt onset of bilateral impaired vision, and arrived to our attention two weeks later. She had a previous episode of mild dizziness. She underwent a fluorescein angiography showing branch retinal artery occlusions and a brain magnetic resonance imaging (MRI) revealing several supraand infratentorial FLAIR-hyperintense white matter lesions, two with contrast enhancement. Thrombophilic, autoimmune and infective (including Human Immunodeficiency Virus, Borrelia burgdorferi, Hepatitis B Virus, Hepatitis C Virus, Herpes Simplex Virus 1-2, Varicella Zoster Virus) screening was negative. Cerebrospinal fluid analysis showed intrathecal IgG synthesis. We suspected a Primary Central Nervous System Vasculitis, and intravenous steroids were started. Three months later a second brain MRI showed seven new lesions without contrast enhancement, and she revealed a cognitive impairment and bilateral hearing loss. Reviewing the clinical history and MRI, she fulfilled diagnostic criteria for Susac syndrome. She had two cycles of cyclophosphamide, and recovered in 6 months and then remained stable with metotrexate.

Quantitative MRI findings indicate diffuse white matter damage in Susac Syndrome.

BackgroundSusac Syndrome (SuS) is an autoimmune endotheliopathy impacting the brain, retina and cochlea that can clinically mimic multiple sclerosis (MS).ObjectiveTo evaluate non-lesional white matter demyelination changes in SuS compared to MS and healthy controls (HC) using quantitative MRI.Methods3T MRI including myelin water imaging and diffusion basis spectrum imaging were acquired for 7 SuS, 10 MS and 10 HC participants. Non-lesional white matter was analyzed in the corpus callosum (CC) and normal appearing white matter (NAWM). Groups were compared using ANCOVA with Tukey correction.ResultsSuS CC myelin water fraction (mean 0.092) was lower than MS(0.11, p = 0.01) and HC(0.11, p = 0.04). Another myelin marker, radial diffusivity, was increased in SuS CC(0.27μm2/ms) compared to HC(0.21μm2/ms, p = 0.008) and MS(0.23μm2/ms, p = 0.05). Fractional anisotropy was lower in SuS CC(0.82) than HC(0.86, p = 0.04). Fiber fraction (reflecting axons) did not differ from HC or MS. In NAWM, radial diffusivity and apparent diffusion coefficient were significantly increased in SuS compared to HC(p < 0.001 for both measures) and MS(p = 0.003, p < 0.001 respectively).ConclusionsOur results provided evidence of myelin damage in SuS, particularly in the CC, and more extensive microstructural injury in NAWM, supporting the hypothesis that there are widespread microstructural changes in SuS syndrome including diffuse demyelination.

Rare Case of Susac Syndrome

Susac syndrome is a rare autoimmune disease affecting the precapillary arteries of the brain, eye and ears causing encephalopathy, branch retinal artery occlusion and sensorineural hearing loss. It is underdiagnosed as it rarely presents with the classic triad. Encephalopathy and branch retinal artery occlusion are curable if the treatment is started early, however the sensorineural hearing loss may be irreversible. The disease course may be monocyclic, polycyclic or chronic. In this review present a case of Susac which was not diagnosed until late in the disease course. Even though the three criteria manifested clinically, the patient was successfully treated. We will also provide a clinical review on the disease based on our research from the literature

Susac syndrome: challenges in the diagnosis and treatment.

Susac syndrome is a disorder thought to be mediated by an autoimmune response towards endothelial cells, leading to a characteristic clinical triad of encephalopathy, visual disturbances due to branch arterial occlusions and sensorineural hearing impairment. Although it is a rare disease, three reasons make it important. First, given its variable presentation, Susac syndrome is underdiagnosed. Second, it is considered an important differential diagnosis in different neurological, psychiatric, ophthalmological and hearing disorders, and consequently is frequently misdiagnosed. Third, in many cases, Susac syndrome is diagnosed and treated late, with significant irreversible sequelae including dementia, blindness and hearing loss. Neuropathology findings derived from both Susac syndrome patient tissue and novel transgenic mouse models indicate cytotoxic CD8+ T cells adhere to microvessels, inducing endothelial cell swelling, vascular narrowing and occlusion, causing microinfarcts. Anti-endothelial cell antibodies are present in serum in 25% of Susac syndrome patients, but it is unclear whether they are aetiologically related to the disease, or an epiphenomenon. The clinical triad comprising encephalopathy, branch arterial occlusions, and sensorineural hearing impairment is considered pathognomonic, although great variability is found in presentation and natural course of disease. At first evaluation, only 13-30% of patients exhibit the full clinical triad, making diagnosis difficult. Retinal fluorescein angiography, optic coherence tomography, MRI and tonal audiometry are helpful methods for diagnosing and monitoring disease activity during treatment. By contrast, there are no reliable objective immune markers to monitor disease activity. Immunosuppression is the current treatment, with high-dose corticosteroid therapy as the mainstay, but additional therapies such as intravenous immunoglobulins, cyclophosphamide, rituximab and mycophenolate mofetil are often necessary, because the disease can be devastating, causing irreversible organ damage. Unfortunately, low rates of disease, variability in presentation and paucity of objective biomarkers make prospective controlled clinical trials for Susac syndrome treatment difficult. Current immunosuppressive treatments are therefore based on empirical evidence, mainly from retrospective case series and expert opinion. In this review, we draw attention to the need to take consider Susac syndrome in the differential diagnosis of different neurological, psychiatric, ophthalmological and hearing disorders. Furthermore, we summarize our current knowledge of this syndrome, in reference to its pathophysiology, diagnosis and management, emphasizing the need for prospective and controlled studies that allow a better therapeutic approach.

A case of nasopharyngeal carcinoma presenting as Susac syndrome

A case of nasopharyngeal carcinoma presenting as Susac syndrome

Hemorrhagic cerebral vasculopathy in Susac syndrome.

Hemorrhagic cerebral vasculopathy in Susac syndrome.

P.080 Cognitive Profile, Disease Characteristics, and Neuroimaging Findings in Susac Syndrome: A Case Series of Seven Participants from British Columbia

Background: Susac Syndrome (SuS) is a rare autoimmune disorder of the cerebral, retinal, and inner ear microvasculature. One of the cardinal manifestations of central nervous system (CNS) involvement is encephalopathy, however the cognitive profile in SuS is poorly characterized in the literature. Methods: In this cross-sectional case series of seven participants diagnosed with Susac Syndrome in remission in British Columbia, we use a battery of neuropsychological testing, subjective disease scores, and objective markers of disease severity to characterize the affected cognitive domains and determine if any disease characteristics predict neuropsychological performance. We also compare this battery of tests to neuroimaging markers to determine if correlation exists between radiographic markers of CNS disease and clinical evaluation of disease severity. Results: There were a variety of cognitive deficits, with memory and language dysfunction being the most common. Despite the variability, performance on some neuropsychological tests (MoCA) correlated to markers of functional disability (EDSS). Additionally, MoCA and EDSS scores correlated with neuroimaging findings of both corpus callosum and white matter changes. Finally, psychiatric scores correlated with participant reported scores of disease severity. Conclusions: There is a relationship between cognitive deficits, subjective and objective disease disability, and neuroimaging findings in Susac Syndrome.

INVESTIGATING MICROANGIOPATHY USING SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH SUSAC SYNDROME.

To determine whether optical coherence tomography angiography is of diagnostic utility for Susac syndrome (SuS) by quantifying microvascular retinal changes. We enrolled 18 eyes of 9 healthy controls and 18 eyes of 9 patients with chronic SuS (12 had previous branch retinal artery occlusions and 6 were clinically unaffected). Images of the fovea were taken using an optical coherence tomography angiography system. Analysis included vessel density, fractal dimension, vessel diameter, and measurements of the foveal avascular zone (area, eccentricity, acircularity index, and axis ratio) in deep and superficial retinal layers. Skeleton density and inner ring vessel density were significantly lower in patients with SuS (skeleton density: Susac 0.11 ± 0.01 vs. controls 0.12 ± 0.01, P = 0.027. VD: SuS 0.39 ± 0.04 vs. controls 0.42 ± 0.02, P = 0.041). Eccentricity and axis ratio were significantly higher in patients with SuS (EC: Susac 0.61 ± 0.11, controls 0.51 ± 0.10, P = 0.003; axis ratio: Susac 1.57 ± 0.28, controls 1.39 ± 0.11, P = 0.005). SuS eyes (affected and unaffected) had poorer outcomes of the remaining vascular parameters compared with controls (P > 0.05). Optical coherence tomography angiography identified chronic microvascular changes in the eyes of patients with chronic SuS. Even clinically unaffected SuS eyes showed poorer vascular parameters. Although further research is needed, this noninvasive imaging modality seems to have the potential to serve as a valuable additive diagnostic tool.

Diagnostic dilemma in Susac syndrome

Susac syndrome is an autoimmune endotheliopathy which specifically affect brain, retina and inner year. The condition is common in young females (20–40 years). The diagnosis is made by presence of encephalopathy, branch retinal artery occlusion and sensory neural hearing impairment. Typical reversible “snow ball” appearance in the central corpus callosum favors the diagnosis. Condition could be successfully treated with IV steroids and Immunoglobulin if identified early.

Manifestation of Susac syndrome during interferon beta-1a and glatiramer acetate treatment for misdiagnosed multiple sclerosis: a case report

BackgroundSusac syndrome (SS) is characterized by the triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. However, the diagnosis of SS remains difficult because the clinical triad rarely occurs at disease onset, and symptom severity varies. SS symptoms often suggest other diseases, in particular multiple sclerosis (MS), which is more common. Misdiagnosing SS as MS may cause serious complications because MS drugs, such as interferon beta-1a, can worsen the course of SS. This case report confirms previous reports that the use of interferon beta-1a in the course of misdiagnosed MS may lead to exacerbation of SS. Moreover, our case report shows that glatiramer acetate may also exacerbate the course of SS. To the best of our knowledge, this is the first reported case of exacerbation of SS by glatiramer acetate.Case presentationWe present a case report of a patient with a primary diagnosis of MS who developed symptoms of SS during interferon beta-1a treatment for MS; these symptoms were resolved after the discontinuation of the treatment. Upon initiation of glatiramer acetate treatment, the patient developed the full clinical triad of SS. The diagnosis of MS was excluded, and glatiramer acetate therapy was discontinued. The patient’s neurological state improved only after the use of a combination of corticosteroids, intravenous immunoglobulins, and azathioprine.ConclusionsThe coincidence of SS signs and symptoms with treatment for MS, first with interferon beta-1a and then with glatiramer acetate, suggests that these drugs may influence the course of SS. This case report indicates that treatment with glatiramer acetate may modulate or even exacerbate the course of SS.

Susac Syndrome: A Rare cause of Bilateral Sensorineural hearing loss from North India-A Case Report with Review of literature.

Susac Syndrome (SS) is a rare unique autoimmune underdiagnosed disorder characterized by the clinical triad of central nervous system (CNS) dysfunction, sensorineural hearing impairment, and branch retinal artery occlusion (BRAO). Objectives The purpose of reporting the case is to succinctly highlight this enigmatic condition with focus on otological and audiological aspect of SS and also to augment awareness of this disease among otolaryngologists neurologists, psychiatrists and ophthalmologists. Additionally we reviewed the otological menifestations and audiological findings related to SS. Methods A case of 38year old female is presented with bilateral SNHL as the initial symptom of SS. The review of otological and audiological findings of previous 10year case reports was executed using the PRISMA protocol on 20 cases. Results It was seen that inspite of the ear being one of the main organs involved in the SS very few had undergone detailed audiological assessment. Our review of literature showed that only 40% cases had done audiological assessment other than PTA, out of which only 5% had undergone complete audiological workup. 30% of the patients were having auditory symptoms as presenting chief complaint. Conclusion Otolyryngologists should keep SS in differentials when a case of SNHL of unknown etiology is encountered.We emphasize the use newer noninvasive Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation diagnostic tools like Optical coherence tomography (OCT), MRI and detailed audiological tests for timely diagnosis of SS. Further multidisciplinary assessment protocols should be used to prevent the development of severe sequelae.

Sudden onset hearing loss as initial presentation of Susac syndrome: a rare case report and brief review

Susac syndrome is a rare disease presenting with a classic triad of symptoms. These are sensorineural hearing loss, encephalopathy, and branch retinal artery occlusions. Initial presentation is usually headache and symptoms of encephalopathy. Hearing loss is unusual in the early stages but, when it does present, can often lead to a misdiagnosis of sudden sensorineural hearing loss. Hence, neurological and retinal examinations are essential to an accurate diagnosis. In this study, we aimed to raise awareness of Susac syndrome among physicians and facilitate recognition of its manifestation, especially in those patients presenting with hearing loss alone. Identifying Susac syndrome that presents as sudden sensorineural hearing loss can be challenging but a number of case reviews have been reported in recent years and treatment guidelines are available.

Brain magnetic resonance imaging lesion load at diagnosis, severity at onset and outcomes in Susac syndrome: A prospective cohort study.

Susac syndrome (SuS) is a rare occlusive microvessel disease of the brain, retina and inner ear. We aimed to determine whether brain lesion load at the acute phase predicts poor outcomes in SuS. A prospective national cohort study was conducted from December 2012 to December 2019 in 20 centres in France. Patients included at the principal investigator's center with available brain magnetic resonance imaging (MRI) at diagnosis were analyzed. MRI was reviewed by an experienced neuroradiologist blinded to clinical status. The size, topography and number of hyperintense lesions on diffusion-weighted imaging (DWI-HL) were analyzed at diagnosis and during follow-up. Outcomes involved descriptive characteristics of patients at onset and last follow-up. Twenty-three patients (38.1 [18.8-56.5] years, 16 females) were prospectively studied. The triad (i.e., brain, eye and ear involvement) was complete at onset in 17 patients. Brain MRI was performed 1.1 (0.1-3.4) months after the first symptom. All patients had DWI-HL at the acute phase. Patients were separated into two groups according to the number of DWI-HL on first MRI: a first group of patients (n=15) displaying low brain lesion load (<50 DWI-HL per patient) and a second group of patients (n=8) displaying high brain lesion load (≥100 DWI-HL). The median follow-up was 57.9 (9.7-98) months. Clinical features, treatment, relapse rate, time to disappearance of DWI-HL, disabilities and professional outcome did not differ according to brain lesion load. Brain lesion load assessed by DWI at the acute phase is not associated with risks of disability in SuS.

WIDEFIELD FLUORESCEIN ANGIOGRAPHY IN THE DIAGNOSIS OF SUSAC SYNDROME.

To present the clinical manifestations and results of key diagnostic investigations in patients with Susac syndrome, with special emphasis on the principal role of fluorescein angiography (FA) of the peripheral retina. A retrospective analysis of medical records (collected 2000-2019) of 20 patients (15 women and five men), aged 20 to 51 years (mean age: 31.6 years) with complete or incomplete Susac syndrome diagnosed by an ophthalmic examination and widefield fluorescein angiography (WF-FA) by Spectralis and Optos Tx200. Fluorescein angiography abnormalities included vascular changes in the posterior pole in 64.7% and in the peripheral retina in 82.4%. Widefield FA abnormalities in the peripheral retina alone were seen in 35.3% and in the posterior pole, but without peripheral vascular involvement, in 17.6%. Secondary leakage from veins was noted in 58.8%. Widefield FA of the peripheral retina has a key role in cases of suspected Susac syndrome as it confirms the diagnosis and assesses disease activity. In addition to the characteristic findings, late-phase FA revealed leakage from veins which is not a typical sign. Patients experiencing migraine headaches may benefit from increasing awareness of neurologists and otologists who more promptly referred patients with suspected Susac syndrome for ophthalmologic evaluation and WF-FA of the peripheral retina.

A Multiple Sclerosis Mimiker with Good Recovery following Specific Therapy: Susac Syndrome

Susac Syndrome (SuS) is a rare disease, characterized by an autoimmune endothelopathy, that involves brain, retina and inner ear. We describe a case of a young woman affected by inner ear-predominant SuS, initially suspected for demyelinating disease, with delayed diagnosis and irreversible hearing ischemic damage, but good prognosis, treated according to current recommendations

ЦЕРЕБРОВАСКУЛЯРНЫЕ ЗАБОЛЕВАНИЯ: ТИПИЧНЫЕ И НЕТИПИЧНЫЕ КЛИНИЧЕСКИЕ ПРОБЛЕМЫ

There is a big number of patients with chronic brain ischemia both among in-patients and out-patients seen by neurologists. This is a typical clinical situation. Retino-cochleo-cerebral vasculopathy (also called Susac syndrome) is a rare autoimmune disorder affecting brain vessels, the 8th cranial nerve and retina. Chronic brain ischemia usually manifests as cognitive decline, affective (emotional) disorders and focal neurological signs. We studied a “portrait” of patients with chronic brain ischemia, admitted to the hospital As in-patient of rehabilitation unit. Here we present the typical case using as an example cerebral ischemic conditions and unusual ones describing retino-cochleo-cerebral vasculopathy as one of the conditions from the group of primary angiitis of central nervous system in adults. All the case were observed by us in neurological and neurorehabilitation wards. It is a pilot project with 43 patients as the total number of patients included into this study. Their mean age was 62.8 years. The mean duration of in-patient observation was 14 days at the hospital. In this paper we discuss the clinical characteristics of our cohort of patients. The least affected here was the short-term memory for numbers. The most affected domain included emotions, anxiety, and depression. We followed this situation in most of our cases. The unusual clinical case of Susac syndrome in a male patient of 59 years is described. The diagnosis was confirmed using modern instrumental tests such as magnetic-resonance tomography and fluorescent angiography of eye retina.

Actualités dans le syndrome de Susac

Susac syndrome is a rare disease affecting mainly young women, characterized by a microangiopathy limited to the cerebral, retinal, and cochlear vessels. Although the pathophysiology of Susac syndrome is not yet fully elucidated, recent advances favour a primitive vasculitis affecting the cerebral, retinal and cochlear small vessels. Susac syndrome must be recognized in the presence of the pathognomonic clinical triad associating: 1/subacute encephalopathy with unusual headache and pseudopsychiatric features associated with diffuse white matter, grey matter nuclei and specifically corpus callosum lesions on brain MRI; 2/eye involvement that may be pauci-symptomatic, with occlusions of the branches of the central artery of the retina at fundoscopy and arterial wall hyperfluorescence on fluorescein angiography; and 3/cochleo-vestibular damage with hearing loss predominating at low frequencies on the audiogram. Relapses are frequent during an active period lasting approximately 2 years. Eventually, the disease resolves but isolated retinal arterial wall hyperfluorescence without new occlusions may recur, which should not lead to treatment intensification. First-line treatment consists of a combination of anti-aggregants and high dose corticosteroids. In refractory patients or in case of relapse, immunomodulatory molecules such as intravenous immunoglobulins or immunosuppressive drugs such as mycophenolate mofetil, cyclophosphamide or rituximab should be started. Unfortunately, sequelae-mostly hearing loss- remain frequent in these young patients.

Susac syndrome with cognitive impairment - case report of 31-year-old woman

Abstract Introduction: Susac syndrome (SuS) is a rare immune-mediated disease caused by occlusions of microvessels in the brain, retina and inner ear. It is characterized by the clinical triad of encephalopathy, visual disturbances and hearing loss. The diagnosis of SuS is based mainly on the clinical symptoms and the supporting tests in which characteristic changes occur in the MRI. Case report: Here, we present a case of a patient with possible SuS with psychiatric symptoms. A 31-year-old woman was admitted to the Department of Psychiatry due to deteriorating mental health for several weeks manifested as a negative mood and suicidal thoughts. During hospitalization, a neurological consultation was conducted, in which the patient was identified as conscious, psychomotor sluggish, with impaired verbal contact and persistent hearing and vision impairment. Cross-sectional assessment of cognitive functions revealed that the patient had a generalized syndrome of neuropsychological deficits, which confirms the diagnosis of dementia. Discussion: This case summary provides an example of a woman diagnosed with SuS manifested as a cognitive impairment with associated vision and hearing deterioration. It is worth emphasizing the fact that such presentation of the triad of at disease onset is rare. The characteristics of the organic changes in the brain described in the MRI probably explain the symptoms described in that case. The prognosis of SuS depends on early diagnosis and treatment. Conclusions: A diagnosis of SuS should always be considered in the presence of nonspecific neuropsychiatric symptoms and progressive multifocal neurological symptoms, hearing loss, and visual impairment. An important fact is that the typical triad of SuS symptoms in most cases does not occur simultaneously, which makes the diagnostic process very difficult and may lead to misdiagnosis.

Fundamental mechanistic insights from rare but paradigmatic neuroimmunological diseases.

The pathophysiology of complex neuroimmunological diseases, such as multiple sclerosis and autoimmune encephalitis, remains puzzling - various mechanisms that are difficult to dissect seem to contribute, hampering the understanding of the processes involved. Some rare neuroimmunological diseases are easier to study because their presentation and pathogenesis are more homogeneous. The investigation of these diseases can provide fundamental insights into neuroimmunological pathomechanisms that can in turn be applied to more complex diseases. In this Review, we summarize key mechanistic insights into three such rare but paradigmatic neuroimmunological diseases - Susac syndrome, Rasmussen encephalitis and narcolepsy type 1 - and consider the implications of these insights for the study of other neuroimmunological diseases. In these diseases, the combination of findings in humans, different modalities of investigation and animal models has enabled the triangulation of evidence to validate and consolidate the pathomechanistic features and to develop diagnostic and therapeutic strategies; this approach has provided insights that are directly relevant to other neuroimmunological diseases and applicable in other contexts. We also outline how next-generation technologies and refined animal models can further improve our understanding of pathomechanisms, including cell-specific and antigen-specific CNS immune responses, thereby paving the way for the development of targeted therapeutic approaches.