-
Neurology(R) Neuroimmunology &... Jul 2023Alteration of the blood-brain barrier (BBB) at the interface between blood and CNS parenchyma is prominent in most neuroinflammatory diseases. In several neurologic...
BACKGROUND AND OBJECTIVES
Alteration of the blood-brain barrier (BBB) at the interface between blood and CNS parenchyma is prominent in most neuroinflammatory diseases. In several neurologic diseases, including cerebral malaria and Susac syndrome, a CD8 T cell-mediated targeting of endothelial cells of the BBB (BBB-ECs) has been implicated in pathogenesis.
METHODS
In this study, we used an experimental mouse model to evaluate the ability of a small-molecule perforin inhibitor to prevent neuroinflammation resulting from cytotoxic CD8 T cell-mediated damage of BBB-ECs.
RESULTS
Using an in vitro coculture system, we first identified perforin as an essential molecule for killing of BBB-ECs by CD8 T cells. We then found that short-term pharmacologic inhibition of perforin commencing after disease onset restored motor function and inhibited the neuropathology. Perforin inhibition resulted in preserved BBB-EC viability, maintenance of the BBB, and reduced CD8 T-cell accumulation in the brain and retina.
DISCUSSION
Therefore, perforin-dependent cytotoxicity plays a key role in the death of BBB-ECs inflicted by autoreactive CD8 T cells in a preclinical model and potentially represents a therapeutic target for CD8 T cell-mediated neuroinflammatory diseases, such as cerebral malaria and Susac syndrome.
Topics: Mice; Animals; Perforin; Neuroinflammatory Diseases; Malaria, Cerebral; Endothelial Cells; Susac Syndrome; Mice, Knockout; CD8-Positive T-Lymphocytes; Disease Models, Animal
PubMed: 37080596
DOI: 10.1212/NXI.0000000000200117 -
Journal of Neuro-ophthalmology : the... Dec 2023Susac syndrome is a vasculopathy, resulting in the classic triad of branch retinal artery occlusion (BRAO), inner ear ischemia, and brain ischemia. In this retrospective...
BACKGROUND
Susac syndrome is a vasculopathy, resulting in the classic triad of branch retinal artery occlusion (BRAO), inner ear ischemia, and brain ischemia. In this retrospective chart review, we characterize fluorescein angiography (FA) findings and other ancillary studies in Susac syndrome, including the appearance of persistent disease activity and the occurrence of new subclinical disease on FA.
METHODS
This multicenter, retrospective case series was institutional review board-approved and included patients with the complete triad of Susac syndrome evaluated with FA, contrasted MRI of the brain, and audiometry from 2010 to 2020. The medical records were reviewed for these ancillary tests, along with demographics, symptoms, visual acuity, visual field defects, and findings on fundoscopy. Clinical relapse was defined as any objective evidence of disease activity during the follow-up period after initial induction of clinical quiescence. The main outcome measure was the sensitivity of ancillary testing, including FA, MRI, and audiometry, to detect relapse.
RESULTS
Twenty of the 31 (64%) patients had the complete triad of brain, retinal, and vestibulocochlear involvement from Susac syndrome and were included. Median age at diagnosis was 43.5 years (range 21-63), and 14 (70%) were women. Hearing loss occurred in 20 (100%), encephalopathy in 13 (65%), vertigo in 15 (75%), and headaches in 19 (95%) throughout the course of follow-up. Median visual acuity at both onset and final visit was 20/20 in both eyes. Seventeen (85%) had BRAO at baseline, and 10 (50%) experienced subsequent BRAO during follow-up. FA revealed nonspecific leakage from previous arteriolar damage in 20 (100%), including in patients who were otherwise in remission. Of the 11 episodes of disease activity in which all testing modalities were performed, visual field testing/fundoscopy was abnormal in 4 (36.4%), MRI brain in 2 (18.2%), audiogram in 8 (72.7%), and FA in 9 (81.8%).
CONCLUSIONS
New leakage on FA is the most sensitive marker of active disease. Persistent leakage represents previous damage, whereas new areas of leakage suggest ongoing disease activity that requires consideration of modifying immunosuppressive therapy.
Topics: Humans; Female; Young Adult; Adult; Middle Aged; Male; Susac Syndrome; Fluorescein Angiography; Retrospective Studies; Retinal Artery Occlusion; Magnetic Resonance Imaging; Retina; Recurrence
PubMed: 37075250
DOI: 10.1097/WNO.0000000000001826 -
Journal of Medical Case Reports Apr 2023Susac syndrome is an immune-mediated, ischemia-producing, occlusive microvascular endotheliopathy that threatens the brain, retina, and inner ear. There is a need for...
BACKGROUND
Susac syndrome is an immune-mediated, ischemia-producing, occlusive microvascular endotheliopathy that threatens the brain, retina, and inner ear. There is a need for disease assessment tools that can help clinicians and patients to more easily, accurately, and uniformly track the clinical course and outcome of Susac syndrome. Ideally, such tools should simultaneously facilitate the clinical care and study of Susac syndrome and improve the value of future case reports. To meet this need, two novel clinical assessment tools were developed: the Susac Symptoms Form and the Susac Disease Damage Score. The former is a comprehensive self-report form that is completed by patients/families to serially document the clinical status of a patient. The latter documents the extent of damage perceived by individual patients/families and their physicians. Both forms were initially trialed with two particularly representative and instructive patients. The results of this trial are shared in this report.
CASE PRESENTATION
Patient 1 is a 21-year-old Caucasian female who presented with an acute onset of headache, paresthesias, cognitive dysfunction, and emotional lability. Patient 2 is a 14-year-old Caucasian female who presented with an acute onset of headache, cognitive dysfunction, urinary incontinence, ataxia, and personality change. Both patients fulfilled criteria for a definite diagnosis of Susac syndrome: both eventually developed brain, retinal, and inner ear involvement, and both had typical "snowball lesions" on magnetic resonance imaging. The Susac Symptoms Form documented initial improvement in both patients, was sufficiently sensitive in detecting a subsequent relapse in the second patient, and succinctly documented the long-term clinical course in both patients. The Disease Damage Score documented minimal disease damage in the first patient and more significant damage in the second.
CONCLUSIONS
The Susac Symptoms Form and the Disease Damage Score are useful disease assessment tools, both for clinical care and research purposes. Their use could enhance the value of future case reports on Susac syndrome and could improve opportunities to learn from a series of such reports.
Topics: Humans; Female; Young Adult; Adult; Adolescent; Susac Syndrome; Brain; Cognitive Dysfunction; Disease Progression; Headache; Magnetic Resonance Imaging
PubMed: 37046335
DOI: 10.1186/s13256-023-03838-9 -
Clinical Rheumatology Jun 2023COVID-19 vaccine circulation approval was a turning point for the coronavirus pandemic. The current approved COVID-19 vaccines, including messenger ribonucleic acid... (Review)
Review
COVID-19 vaccine circulation approval was a turning point for the coronavirus pandemic. The current approved COVID-19 vaccines, including messenger ribonucleic acid (mRNA)-based and adenovirus vector-based vaccines, were shown to significantly reduce the disease mortality and severity, and its adverse reactions are mainly mild ones. However, few cases of autoimmune conditions, both flare-ups and new-onset, were described in association with these vaccines. Susac vasculitis (SaS) is a rare autoimmune disease characterized by the clinical triad of encephalopathy, visual disturbances, and sensorineural hearing loss. Its pathogenesis is still not fully understood but is believed to be related to autoimmune processes, including autoantibodies to anti-endothelial cells and cellular immune processes that lead to microvascular damage and, consequently, micro-occlusions of the cerebral, inner ear, and retinal vessels. It has been previously described following vaccination and, most recently, few cases following coronavirus vaccines. We here describe a case of a previously healthy 49-year-old man diagnosed with SaS 5 days following the first dose of the BNT162b2 COVID-19 vaccine.
Topics: Humans; Male; Middle Aged; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Magnetic Resonance Imaging; Susac Syndrome; Vaccination
PubMed: 36877303
DOI: 10.1007/s10067-023-06564-1 -
Retinal Cases & Brief Reports Mar 2023Susac syndrome consists of the triad of encephalopathy, branch retinal artery occlusion, and hearing loss and is believed to be an immune-mediated endotheliopathy....
BACKGROUND
Susac syndrome consists of the triad of encephalopathy, branch retinal artery occlusion, and hearing loss and is believed to be an immune-mediated endotheliopathy. Arteriolar wall hyperfluorescence (AWH) on retinal fluorescein angiography (FA) has been described in the literature as a classic ophthalmic sign for Susac syndrome. In this article, we report a pattern of distally shifting segments of AWH on FA over time that was observed in two cases.
METHODS
Two cases of Susac syndrome are presented with an emphasis on FA findings, obtained at frequent intervals during follow-up.
RESULTS
In both cases, FA displays a shifting pattern of segments of AWH distal to the localization of the AWH observed on the previous FA.
CONCLUSION
In patients with Susac syndrome, FA plays an important role in aiding diagnosis and monitoring the efficacy of treatment and disease activity during follow-up. In these two cases, the angiography revealed how the AWH can migrate along the vessel over time. This is the first published report showing an evolving distally shifting pattern of AWH in patients with Susac syndrome.
Topics: Humans; Susac Syndrome; Fluorescein Angiography; Retinal Artery Occlusion; Magnetic Resonance Imaging
PubMed: 36821470
DOI: 10.1097/ICB.0000000000001131 -
AJNR. American Journal of Neuroradiology Mar 2023Susac syndrome is a rare disorder affecting the brain, retina, and inner ear, probably triggered by an immune-mediated endotheliopathy. Diagnosis is based on clinical...
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.
Topics: Humans; Susac Syndrome; Magnetic Resonance Imaging; Brain; Retina; Ear, Inner
PubMed: 36797034
DOI: 10.3174/ajnr.A7801 -
Journal of the Academy of... 2023
Topics: Humans; Susac Syndrome; Valproic Acid
PubMed: 36764750
DOI: 10.1016/j.jaclp.2022.09.005 -
SAGE Open Medical Case Reports 2023Susac syndrome is a rare microangiopathy of indeterminate etiology, presumably autoimmune, characterized by a triad of encephalopathy, sensorineural hearing loss, and...
Susac syndrome is a rare microangiopathy of indeterminate etiology, presumably autoimmune, characterized by a triad of encephalopathy, sensorineural hearing loss, and branch retinal artery occlusions occurring predominantly in women. The onset and progression patterns are multiple, mainly of three modes. Fulminant evolution is exceptional, rarely reported across literature. We report through this case a Susac syndrome in a young man in whom evolution was fatal. Magnetic resonance imaging is essential to raise the diagnosis and for follow-up, with almost pathognomonic findings, all the more useful as the clinical triad is usually incomplete and as the encephalopathy is the most limiting of the symptoms.
PubMed: 36756223
DOI: 10.1177/2050313X221149826 -
Journal of Neuroimmunology Mar 2023Susac syndrome (SuS) is a rare immune-mediated endotheliopathy that affects the brain, retina and inner ear and is characterised by the variable clinical triad of...
Susac syndrome (SuS) is a rare immune-mediated endotheliopathy that affects the brain, retina and inner ear and is characterised by the variable clinical triad of encephalopathy, visual and vestibulocochlear dysfunction. Here, we present clinical and paraclinical data of 19 SuS patients followed at Ghent University Hospital and highlight some atypical clinical and novel radiological findings. Our findings suggest that spinal involvement expands the clinical phenotype of SuS. We further introduce dark blood sequences as a more sensitive technique to detect radiological disease activity in SuS. Our data add to the current understanding of the diagnosis, monitoring and treatment of SuS.
Topics: Humans; Susac Syndrome; Magnetic Resonance Imaging; Brain; Brain Diseases; Retina
PubMed: 36736020
DOI: 10.1016/j.jneuroim.2023.578032 -
Otolaryngologia Polska = the Polish... Jan 2023Susac syndrome is a rare autoimmune vasculopathy involving the small precapillary arterioles of the brain, retina, and inner ear. It is characterized by a triad of... (Review)
Review
Susac syndrome is a rare autoimmune vasculopathy involving the small precapillary arterioles of the brain, retina, and inner ear. It is characterized by a triad of symptoms: encephalopathy, visual disturbances due to obstruction of retinal artery branches, and sensorineural hearing loss. The study aimed to review the current medical knowledge on Susac syndrome and present our clinical experience regarding this disease entity. The paper also presents a case of a 25-year-old patient who was diagnosed with Susac's syndrome based on the clinical picture and the results of additional tests. This syndrome should be considered in the differential diagnosis of multiple sclerosis and other multifocal lesions of the central nervous system because early diagnosis of the disease and immunosuppressive treatment significantly alleviates its course and improves the prognosis.
Topics: Humans; Adult; Susac Syndrome; Magnetic Resonance Imaging; Brain; Hearing Loss, Sensorineural; Prognosis; Diagnosis, Differential
PubMed: 36718572
DOI: No ID Found