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Journal of Neurology Dec 2023Susac 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...
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.
Topics: Humans; Susac Syndrome; Follow-Up Studies; Brain; Retinal Artery Occlusion; Magnetic Resonance Imaging
PubMed: 37608221
DOI: 10.1007/s00415-023-11891-z -
Neurology(R) Neuroimmunology &... May 2024Susac syndrome (SuS) is an orphan microangiopathic disease characterized by a triad of encephalopathy, visual disturbances due to branch retinal artery occlusions, and... (Review)
Review
Susac syndrome (SuS) is an orphan microangiopathic disease characterized by a triad of encephalopathy, visual disturbances due to branch retinal artery occlusions, and sensorineuronal hearing loss. Our previous systematic review on all cases of SuS reported until 2012 allowed for a better understanding of clinical presentation and diagnostic findings. Based on these data, we suggested diagnostic criteria in 2016 to allow early diagnosis and treatment of SuS. In view of the accumulation of new SuS cases reported in the last 10 years and improved diagnostic tools, we here aimed at updating the demographic and clinical features of SuS and to review the updated ancillary tests being used for SuS diagnosis. Therefore, based on the 2016 criteria, we systematically collected and evaluated data on SuS published from January 2013 to March 2022.
Topics: Humans; Susac Syndrome; Magnetic Resonance Imaging; Brain Diseases; Vision Disorders; Diagnosis, Differential
PubMed: 38364193
DOI: 10.1212/NXI.0000000000200209 -
Frontiers in Immunology 2023CD8+ lymphocytes are adaptive immunity cells with the particular function to directly kill the target cell following antigen recognition in the context of MHC class I.... (Review)
Review
CD8+ lymphocytes are adaptive immunity cells with the particular function to directly kill the target cell following antigen recognition in the context of MHC class I. In addition, CD8+ T cells may release pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and a plethora of other cytokines and chemoattractants modulating immune and inflammatory responses. A role for CD8+ T cells has been suggested in aging and several diseases of the central nervous system (CNS), including Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, limbic encephalitis-induced temporal lobe epilepsy and Susac syndrome. Here we discuss the phenotypic and functional alterations of CD8+ T cell compartment during these conditions, highlighting similarities and differences between CNS disorders. Particularly, we describe the pathological changes in CD8+ T cell memory phenotypes emphasizing the role of senescence and exhaustion in promoting neuroinflammation and neurodegeneration. We also discuss the relevance of trafficking molecules such as selectins, mucins and integrins controlling the extravasation of CD8+ T cells into the CNS and promoting disease development. Finally, we discuss how CD8+ T cells may induce CNS tissue damage leading to neurodegeneration and suggest that targeting detrimental CD8+ T cells functions may have therapeutic effect in CNS disorders.
Topics: Humans; CD8-Positive T-Lymphocytes; Cytokines; Central Nervous System; Amyotrophic Lateral Sclerosis
PubMed: 37575227
DOI: 10.3389/fimmu.2023.1233870 -
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 -
Cureus Nov 2023Susac syndrome is a relatively uncommon autoimmune disease that predominantly affects young females, with the highest incidence between the third and fourth decade of...
Susac syndrome is a relatively uncommon autoimmune disease that predominantly affects young females, with the highest incidence between the third and fourth decade of life, presenting classically with encephalopathy, various CNS dysfunctions, visual impairment due to retinal artery occlusion, and hearing loss. Despite treatment options, such as glucocorticoid steroids, intravenous immunoglobulin, methotrexate, azathioprine, mycophenolate mofetil, or rituximab, some patients with Susac syndrome remain refractory to therapy. We present a case report of a 38-year-old female with refractory Susac syndrome who was treated successfully with plasmapheresis.
PubMed: 38098926
DOI: 10.7759/cureus.48811 -
Journal of Clinical Neurology (Seoul,... Sep 2023
PubMed: 37635426
DOI: 10.3988/jcn.2022.0477 -
Journal of Surgical Case Reports Oct 2023Susac syndrome (SS) is a rare microangiopathy affecting the precapillary arterioles of the brain, inner ear, and retina. We present a novel case of SS, presenting as...
Susac syndrome (SS) is a rare microangiopathy affecting the precapillary arterioles of the brain, inner ear, and retina. We present a novel case of SS, presenting as acute incomplete bitemporal field loss in addition to temporally spaced neurological and vestibulocochlear symptoms. A 39-year-old female was referred to the ophthalmology clinic with acute incomplete bitemporal hemianopia and worsening hemicrania. History revealed progressive hearing loss, subjective short-term memory impairment, and vertigo temporally spaced over the preceding 12 months. Magnetic resonance brain revealed multiple small colosal lesions and liner 'spoke' lesions. Fundus fluorescein angiography revealed multiple branch retinal artery occlusions in the right eye. Audiometry confirmed bilateral sensorineural hearing loss. Treatment included intravenous corticosteroids and rituximab. This case highlights the importance of early consideration and evaluation of SS in individuals presenting with atypical ocular disturbances, where no clear cause can be elicited, in order to limit the sequelae of disease.
PubMed: 37867919
DOI: 10.1093/jscr/rjad541 -
Neurology(R) Neuroimmunology &... May 2024
PubMed: 38593388
DOI: 10.1212/NXI.0000000000200247 -
Oman Journal of Ophthalmology 2023
PubMed: 38059113
DOI: 10.4103/ojo.ojo_330_22 -
Frontiers in Neurology 2023Susac syndrome (SS) is a rare immune-mediated vasculitis affecting retina, inner ear and brain. Assessment of central nervous system (CNS) involvement is currently based...
BACKGROUND
Susac syndrome (SS) is a rare immune-mediated vasculitis affecting retina, inner ear and brain. Assessment of central nervous system (CNS) involvement is currently based on standard brain magnetic resonance imaging (MRI) sequences. Accuracy of three dimensional (3D)-vessel wall imaging (VWI) was compared to standard sequences and contrast-enhanced-3D T2-fluid attenuated inversion recovery (CE-FLAIR) to assess CNS disease activity in two cases of definite SS.
METHODS
Brain MRI scan and retinal fluorescein angiogram (RFA) were performed at disease onset and at 1, 3, and 6 months after induction therapy start. CE-FLAIR and VWI based on 3D black-blood proton density weighted (PDW) with and without gadolinium were added to standard sequences on a 3 Tesla MRI scanner.
RESULTS
Contrast enhanced-VWI (CE-VWI) detected an abnormal diffuse leptomeningeal enhancement (LME) in both cases at onset and during follow-up. Pathological enhancement on CE-VWI persisted at 6-month brain MRI, despite absence of new lesions and disappearance of LME on CE-FLAIR. Follow-up RFA revealed new arterial wall hyperfluorescence in both cases.
CONCLUSIONS
VWI may represent a useful tool for diagnosing and monitoring CNS disease activity in SS patients, as confirmed by concordance with RFA, leading treatment's choice and timing. Moreover, CE-VWI seemed at least as sensitive as CE-FLAIR in detecting LME, possibly being superior to the latter in posterior fossa. LME remission might be not accurate in predicting suppression of CNS inflammation in SS.
PubMed: 37638191
DOI: 10.3389/fneur.2023.1201643