Central intra-lesional iron deposits as a possible novel imaging marker at 7 Tesla MRI in Susac Syndrome - an exploratory study.

BACKGROUND: Susac syndrome (SuS) is a rare autoimmune disease that leads to hearing impairment, visual field deficits, and encephalopathy due to an occlusion of precapillary arterioles in the brain, retina, and inner ear. Given the potentially disastrous outcome and difficulties in distinguishing SuS from its differential diagnoses, such as multiple sclerosis (MS), our exploratory study aimed at identifying potential new SuS-specific neuroimaging markers. METHODS: Seven patients with a definite diagnosis of SuS underwent magnetic resonance imaging (MRI) at 7 Tesla (7T), including T2* weighted and quantitative susceptibility mapping (QSM) sequences. T2 weighted hyperintense lesions were analyzed with regard to number, volume, localization, central vein sign, T1 hypointensity, and focal iron deposits in the center of SuS lesions ("iron dots"). Seven T MRI datasets from the same institute, comprising 75 patients with, among others, MS, served as controls. RESULTS: The "iron dot" sign was present in 71.4% (5/7) of the SuS patients, compared to 0% in our control cohort. Thus, sensitivity was 71.4% and specificity 100%. A central vein sign was only incidentally detected. CONCLUSION: We are the first to demonstrate this type of "iron dot" lesions on highly resolving 7T T2*w and QSM images in vivo as a promising neuroimaging marker of SuS, corroborating previous histopathological ex vivo findings.

Susac syndrome: neurological update (clinical features, long-term observational follow-up and management of sixteen patients).

Susac syndrome is a likely autoimmune microangiopathy affecting the brain, retina and inner ear. Due to the rarity of this condition, diagnosis and treatment can be challenging. Diagnosis is based on the presence of the clinical triad of central nervous system dysfunction, branch retinal artery occlusions and sensorineural hearing loss. Typical MRI findings of callosal and peri-callosal lesions may assist in diagnosis. Clinical course can be monophasic, polycyclic or chronic continuous. It is important to look out for red flags to attain an accurate diagnosis and follow a therapeutic algorithm based on severity of the disease and response to treatment. Patients are treated with steroids and immunosuppressive agents with a variable response. Early aggressive treatment especially in severe cases, may help in preventing relapses and morbidity/disability. This study highlights important diagnostic features and proposes a treatment algorithm based on clinical experience from management of 16 patients from 2 neuroscience centres in the UK since 2007, who were followed up over a long period of 3-15 years.

Leptomeningeal Interfoliar Enhancement on Vessel Wall MR Imaging as a Unique Radiologic Finding of Susac Syndrome.

Susac syndrome is a rare disorder affecting the brain, retina, and inner ear, probably triggered by an immune-mediated endotheliopathy. Diagnosis is based on clinical presentation and ancillary test findings (brain MR imaging, fluorescein angiography, and audiometry). Recently, vessel wall MR imaging has shown increased sensitivity in the detection of subtle signs of parenchymal, leptomeningeal, and vestibulocochlear enhancement. In this report, we describe a unique finding identified using this technique in a series of 6 patients with Susac syndrome and discuss its potential value for diagnostic work-up and follow-up.

Susac's syndrome - the crucial role of imaging tests for proper diagnosis.

INTRODUCTION: Susac's syndrome (SS) is a rare, autoimmune-mediated endoteliopathy characterized by a clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. SS is also characterized by a neuroimaging triad consisting of white matter lesions, grey matter lesions, and leptomeningeal enhancement on magnetic resonance imaging (MRI). Considering the rarity of SS, as well as certain similarity to other, more frequent neurological diseases, such as multiple sclerosis (MS), this syndrome is sometimes incorrectly diagnosed and treated. OBJECTIVE: The aim of the study is to present the current state of knowledge on SS, with particular consideration for the differential diagnostics between SS and MS, using the latest available imaging techniques, such as brain MRI, optical coherence tomography (OCT), OCT angiography (OCTA) and fluorescein angiography (FA). REVIEW METHODS: The major electronic databases (PubMed, Google Scholar) were searched manually in order to identify the relevant studies published on SS. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Distinguishing SS from MS is a diagnostic challenge. In the majority of cases, patients with SS do not present the complete clinical or neuroimaging triad, and a delay in making the correct diagnosis exposes the patient to the occurrence of complications, resulting from the development of the underlying disease, or/and the application of improper treatment. In the case of SS the results of brain MRI and FA are essential for making the correct diagnosis as they may reveal pathognomonic changes. SUMMARY: Imaging examinations, such as brain MRI, FA, and OCT complement each other, due to which the diagnosis of SS may be simpler, irrespective of the stage of the disease.

Susac syndrome: The importance of an early diagnosis.

A 38-year-old man who attended the emergency department with headache, accompanied by vomiting, bradypsychia and gait instability, for which he was admitted to Neurology for study. During his admission, he began to present bilateral hearing loss and blurred vision in the left eye, with areas of arterial occlusion and hyperfluorescence of the arterial wall being observed in the ophthalmological examination. As a result, he was diagnosed with Susac syndrome. He was treated with systemic corticosteroids, as well as with rituximab and subsequently, with intravenous immunoglobulins and mycophenolate mofetil. The patient managed to preserve visual acuity, with gait instability and bilateral hearing loss as sequelae. Early diagnosis of Susac syndrome is important, because a delay in the start of treatment can lead to irreversible sequelae such as deafness, blindness or neurological involvement.

Síndrome de Susac: la importancia de un diagnóstico precoz / Susac syndrome: The importance of an early diagnosis

Varón de 38 años que acude a urgencias con cefalea, acompañada de vómitos, bradipsiquia e inestabilidad de la marcha, por lo que ingresa en neurología para estudio. Durante el ingreso, comienza con hipoacusia bilateral y visión borrosa en el ojo izquierdo, apreciándose en la exploración oftalmológica áreas de oclusión arterial e hiperfluorescencia de la pared arterial, por lo que es diagnosticado de síndrome de Susac. Se realiza tratamiento con corticoides sistémicos, así como con rituximab, y posteriormente con inmunoglobulinas intravenosas y micofenolato de mofetilo. El paciente consigue preservar la agudeza visual y presenta como secuelas, inestabilidad de la marcha y pérdida de audición bilateral. El diagnóstico precoz del síndrome de Susac es importante, porque un retraso en el inicio del tratamiento puede dar lugar a secuelas irreversibles como sordera, ceguera o afectación neurológica (AU)

A 38-year-old man who attended the emergency department with headache, accompanied by vomiting, bradypsychia and gait instability, for which he was admitted to Neurology for study. During his admission, he began to present bilateral hearing loss and blurred vision in the left eye, with areas of arterial occlusion and hyperfluorescence of the arterial wall being observed in the ophthalmological examination. As a result, he was diagnosed with Susac syndrome. He was treated with systemic corticosteroids, as well as with rituximab and subsequently, with intravenous immunoglobulins and mycophenolate mofetil. The patient managed to preserve visual acuity, with gait instability and bilateral hearing loss as sequelae. Early diagnosis of Susac syndrome is important, because a delay in the start of treatment can lead to irreversible sequelae such as deafness, blindness or neurological involvement (AU)

Susac syndrome with the typical clinical triad: A case report and literature review.

Susac syndrome is an immune-mediated microvascular disease characterized by the clinical triad of acute multiple encephalopathies, branch retinal artery occlusion, and sensorineural hearing loss. However, the typical clinical triad is not seen in all patients at disease onset. In this study, a 29-year-old male was admitted to our hospital due to aggravation of headache accompanied by retarded reaction. After treatment for a diagnosis of possible central nervous system vasculitis, the patient's retarded reaction and neurological dysfunction were improved. One year after discharge, the patient had no abnormal clinical symptoms and he discontinued taking prednisone voluntarily five months after discharge. Two years later, the patient was admitted to our hospital again owing to a sudden visual field defect in the superonasal quadrant of the left eye for one week, and Susac syndrome was diagnosed. After treatment, the patient's condition became stabilized with no further progress, but the visual field defect did not recover. At the onset of Susac syndrome, the typical clinical triad of Susac syndrome is rare, so this disease is difficult to be recognized at the beginning. The case we report presented the clinical triad two years after the disease onset. We expect that this case report will increase physicians' understanding of Susac syndrome.

Susac syndrome with a unique involvement of the thoracic spinal cord.

A woman in her late 20s presented with headaches and subacute encephalopathy. MRIs showed multiple punctate subcortical and periventricular white matter hyperintensities with diffusion restriction, infratentorial lesions, leptomeningeal enhancement of the cervical spinal cord, brainstem and cerebellum and two areas of high-signal abnormality at T4 and T6 raising suspicion for multiple sclerosis or acute disseminated encephalomyelitis.Further studies and evolution of her symptoms during her hospital stay confirmed the clinical triad of encephalopathy, branch retinal artery occlusions and hearing loss pathognomonic for Susac's syndrome.While cervical spinal cord and cauda equina involvement have been reported in Susac's syndrome previously, no thoracic spinal cord involvement has been reported.We report the novel MRI finding of thoracic spinal cord involvement in Susac's syndrome. In order to avoid misdiagnosis, neurologists and neuroradiologists should be aware that any part of the spinal cord can be involved in Susac's syndrome.

Susac's syndrome diagnostic difficulties - the neurological point of view.

Susac's syndrome is a rare microangiopathy affecting small vessels of the retina, inner ear and brain. It is characterised by a triad of symptoms: encephalopathy, visual defects, and sensorineural hearing loss. The disease is probably caused by an autoimmune process. Diagnosis is based on the typical symptoms, brain MRI, and, most importantly, fluorescein angiography. It is important to distinguish between Susac's syndrome and multiple sclerosis or migraine with aura, because misdiagnosis leads to the wrong treatment. To date, no detailed guidelines for the treatment of Susac's syndrome have been developed. Immunosuppression seems to be effective. It must be remembered that early and aggressive treatment is crucial, and that delays in diagnosis, and as a result in treatment implementation, worsen the prognosis.

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.

Leptomeningeal enhancement on post-contrast FLAIR images for early diagnosis of Susac syndrome.

BACKGROUND: Leptomeningeal enhancement (LME) is a key feature of Susac syndrome (SuS) but is only occasionally depicted on post-contrast T1-weighted images (T1-WI). OBJECTIVE: As post-contrast fluid-attenuated inversion recovery (FLAIR) may be more sensitive, our aim was to assess LME in SuS on this sequence. METHODS: From 2010 to 2020, 20 patients with definite SuS diagnosis were retrospectively enrolled in this multicentre study. Two radiologists independently assessed the number of LME on post-contrast FLAIR and T1-WI acquisitions performed before any treatment. A chi-square test was used to compare both sequences and the interrater agreement was calculated. RESULTS: Thirty-five magnetic resonance imagings (MRIs) were performed before treatment, including 19 post-contrast FLAIR images in 17 patients and 25 post-contrast T1-WI in 19 patients. In terms of patients, LME was observed on all post-contrast FLAIR, contrary to post-contrast T1-WI (17/17 (100%) vs. 15/19 (79%), p < 0.05). In terms of sequences, LME was observed on all post-contrast FLAIR, contrary to post-contrast T1-WI (19/19 (100%) vs. 16/25 (64%), p < 0.005). LME was disseminated at both supratentorial (19/19) and infratentorial (18/19) levels on post-contrast FLAIR, contrary to post-contrast T1-WI (3/25 and 9/25, respectively). Interrater agreement was excellent for post-contrast FLAIR (κ = 0.95) but only moderate for post-contrast T1-WI (κ = 0.61). CONCLUSION: LME was always observed and easily visible on post-contrast FLAIR images prior to SuS treatment. In association with other MRI features, it is highly indicative of SuS.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Brain lesion load assessed by DWI at the acute phase is not associated with risks of disability in SuS.

A rare presentation of Susac syndrome: Report of three pediatric cases.

Susac syndrome is a rare disorder that is clinically characterized by encephalopathy, retinopathy and hearing loss. Most of the reported cases in the literature are adult patients, pediatric presentation is extremely rare. Here we present three pediatric patients aged between 10-15; diagnosed as Susac syndrome. They all had thalamic involvement in addition to typical callosal lesions. All of the three patients had a monophasic course and good treatment response.

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.

Multimodal Imaging in Susac Syndrome: A Case Report and Literature Review.

Susac syndrome (SS) is a rare microangiopathy that involves arterioles of the brain, retina, and cochlea. Diagnosis is extremely difficult because of the rarity of the disease and because the signs and symptoms often occur at different times. Multidisciplinary approaches and multimodal images are mandatory for diagnosis and prompt therapy. In this report, we describe a case of SS and the application of multimodal retinal imaging to evaluate the ophthalmologic changes and to confirm diagnosis. Early diagnosis and therapy based on the associations of steroids and immunosuppressants are necessary to limit the sequelae of the disease.