Inclusion in an NLM database does not imply endorsement of, or agreement with, Susac's syndrome (SS) is a relatively rare cause of multiple recurrent branch retinal arterial occlusions (BRAO). Susac syndrome classically consists of a clinical triad of: acute or subacute encephalopathy which could manifest in a broad spectrum of symptoms, e.g. The mean follow-up time was 3525.58 months (range 1653 months). Cador-Rousseau B, Cazalets C, Decaux O, et al. 17. All patients diagnosed as having Susac syndrome and treated at a tertiary medical center (Sheba Medical Center, Tel Hashomer, Israel) between 1998 and 2014 were included. Susac Syndrome is an extremely rare disorder which is characterized by abnormalities in the three most major organs of the body which is the brain, the eyes, and the ears. (A) Corpus callosum lesions (arrows). Successful Treatment of Incomplete Susac Syndrome with Simultaneous ENT examination revealed nystagmus on lateral gaze with a negative Rombergs and Unterbergs test. The neuro-otology of Susac syndrome | SpringerLink 14 Citations 1 Altmetric Metrics Abstract Background Susac syndrome (SuS) is a rare condition characterized by a clinical triad of sensorineural hearing loss, branch artery occlusion and encephalopathy. Careers, Unable to load your collection due to an error. Snellen VA was converted to log MAR values. In addition to the corpus callosum, lesions can also involve the periventricular white matter, centrum semiovale, cerebellum, brainstem, and middle cerebellar peduncles 13. government site. Radiology. The exact aetiology is unknown. AJNR Am J Neuroradiol. All data relevant to the study are included in the article. Susac JO, Hardman JM, Selhorst JB. Correspondence to: Anuoluwapo R. Oke, Rheumatology Department, Great Western Hospital, Marlborough Road, Swindon SN3 6BB, UK. Noteworthy, patients that fall into the categories of suspected Susac syndrome and incomplete Susac syndrome may fulfill the criteria of other diagnoses as well. The organs involved can easily become irreversibly dama Case records of the Massachusetts General Hospital. MRI of Susac's syndrome. Susac syndrome causes your immune system to attack the network of small blood vessels in your inner ear, retina and brain. [1315] Autoimmune diseases are usually more prevalent in females, and Susac syndrome was similarly found in previous studies to be more common in females, with a male/female ratio of 1:3.5. To date, there are no therapeutic guidelines for Susac syndrome. Its only after recurrence of the illness during steroid tapering, and the emergence of other clinical features of SS, which an accurate diagnosis can be made.17 Many experts suggest consultation with a neuro-ophthalmologist or retinal specialist for detecting Gass plaques, in all patients with unexplained encephalopathy, to prevent misdiagnosis.19 There is no specific test for diagnosis of SS and the diagnosis should be made by characteristic clinical triad and exclusion of other conditions.10,15. Insurance benefit, including Managed Care or federal reimbursements, cannot be combined with any of our promotional offers, coupons or discounts. Rennebohm R, Susac JO, Egan RA, Daroff RB. However, when lesions of the corpus callosum are observed, as seen in all of our cases, the suspicion of Susac syndrome should be high, especially when there are coexisting auditory or BRAO problems. Diagnostic criteria have been proposed in 2016 that divide patients into definite and probable diagnosis of Susac syndrome based on the presence of certain clinical and imaging criteria 18. Patient Sentiment toward Non-Medical Drug Switching, New Poll Reveals Chronic Disease Patients Thoughts on COVID and Related Access and Safety, Rethinking What it Means to Exercise with Ankylosing Spondylitis, Why the COVID-19 Virus Keeps Mutating and What It Means for You. Dorr J, Krautwald S, Wildemann B, Jarius S, Ringelstein M, Duning T, et al. What Is Susac Syndrome? - iCliniq 8. Susac syndrome symptoms overlap with various rheumatic diseases; awareness is crucial for prompt Multidisciplinary team collaboration. As a company focused on care, our Anderson Audiology team is committed to providing a safe and healthy environment for our customers and staff. Other important differentials include multiple sclerosis, given the female preponderance and age of onset, Menieres disease, Lymes disease, encephalitis and stroke. Mateen FJ, Zubkov AY, Muralidharan R, et al. The overall significance level was set to an alpha of 0.05. This shows characteristic T2 hyperintensity changes in the central portion of the corpus callosum, termed snowballs, which are best seen on sagittal T2 FLAIR images (Fig. Laryngoscope. It also explains your rights regarding your data, and how you can exercise those rights. Signal characteristics of all of these lesions include: T1: lesions are low signal, especially in the chronic stage (see T1 black holes)1,2,8,11, T1 C+ (Gd):lesions frequently enhance during the acute stage 1,2,8,11, T2/FLAIR:lesions are high signal 1,2,8,11, DWI/ADC: high DWI signal, facilitated diffusion 1,2,8. Given that it is a rare disease, no consensus on effective therapy is available. Products demonstrated may differ from products sold. Epub 2007 Feb 28. Susac syndrome was first described by Susac et al. Hearing instruments may not meet the needs of all hearing-impaired individuals. the contents by NLM or the National Institutes of Health. Peripheral numbness is rarely reported in Susac syndrome. Generally, diagnosis requires at least two areas of your body to be affected by reported symptoms. The condition is characterized by three main symptoms: brain disease (encephalopathy), hearing loss, and vision loss. It is caused by a microangiopathy affecting the arterioles of the brain, retina, and cochlea, giving the classic clinical triad of subacute encephalopathy, visual loss secondary to retinal branch occlusions, and sensorineural hearing loss. Here, we have a short discussion on this issue to introduce it to our colleagues and remind it as a differential diagnosis in patients with unexplained encephalopathy. It may occur in areas remote from the occluded arterioles. These require cerebral MRI with contrast, fluorescein angiography and audiometry. 9. She was diagnosed with Susac syndrome based on her symptoms and these findings. 2009;119 (1): 141-4. 1C). The symptoms of Susac syndrome can mimic diseases, including multiple sclerosis or chronic encephalitis. The pathologic findings of brain biopsies from most of the case reports showed multiple microinfarctions of the brainstem, both grey and white matter, with the loss of axons, neurons and myelin in the lesions. Susac syndrome (SuS) is a rare and presumably autoimmune mediated disease affecting the small arterial vessels of the brain, inner ear and retina. The involvement of the three systems characterizes the "complete" triad of encephalopathy, BRAO and sensori-neural hearing loss [] that could develop over years.Subclinical pathology occurs in a substantial number of patients sometimes causing a delay in . [9] In our current series, the male/female ratio was 1:1.5. The corpus callosum in the diagnosis of multiple sclerosis and other CNS demyelinating and inflammatory diseases. Oliveira P, Mayeux J. Tumour necrosis factor (TNF) inhibitor therapy in Susac's syndrome. Susac syndrome. Today, were taking a closer look at this rare disorder, including causes and treatment options. Susac's syndrome: an update | British Journal of Ophthalmology This field is for validation purposes and should be left unchanged. Radiographic imaging Temporal bone histopathology Susac syndrome treatment Susac syndrome prognosis Susac syndrome Susac syndrome is a rare autoimmune disorder characterized by the clinical triad of encephalopathy, sensorineural hearing loss, and visual disturbance resulting from branch retinal artery occlusion (BRAO) 1. Coppeto JR, Currie JN, Monteiro ML, et al. 2004;25 (3): 351-2. Susac syndrome is an autoimmune condition that affects the very small blood vessels in the brain, retina, and inner ear (cochlea). 2005;18 (3): 311-4. She later presented to the eye department with sudden onset painless visual field defect in her left eye. We would like to thank Dr. M.A. We do not knowingly collect user data from minors. Symptoms vary from person to person. Crawley BK, Close A, Canto C et-al. Otologic manifestations of Susac syndrome - PMC - National Center for Table Table22 summarizes the signs at presentation of each patient. 20. ADVERTISEMENT: Supporters see fewer/no ads. As a library, NLM provides access to scientific literature. All male patients in the series developed the full triad. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (, Susac Syndrome, Branch Retinal Artery Occlusion, Sensorineural Hearing Loss. AJNR Am J Neuroradiol. The study was approved by the local institutional review board (IRB) of Sheba Medical Center. These are caused by slow extravasation of blood lipids into the arteriolar wall at the site of arteriolar wall damage. In summary, this retrospective case series examined the characteristics of Susac syndrome and the patients long-term outcomes. Bethesda, MD 20894, Web Policies The syndrome was manifested as a full triad on presentation only in males, a finding that may indicate that although it is more prevalent in females, it is more severe in males. Treatment of inner ear symptoms in Susac syndrome requires further research as early immunotherapy may be beneficial. MRI findings in Susac's syndrome. Before A syndrome of arterial-occlusive retinopathy and encephalopathy, A syndrome of brain, inner ear and retinal microangiopathy, Microangiopathy of the brain, retina, and ear: improvement without immunosuppressive therapy. Only 2 patients presented with the full triad and 7 patients developed the full triad during mean follow-up period of 35 months. The .gov means its official. National Library of Medicine At the time the article was last revised Rohit Sharma had The mean MD on the VF defect study at the end of follow-up was 9.117.94 (range 22.61 to 4.3.62) in the right eye and 10.266.60 (range 18.85 to 1.44) in the left eye. Skin involvement in Susac's syndrome. The limitations of the study include its small size and retrospective nature. The condition more commonly affects females around the 2nd to 4th decades 1. The BRAO may be extensive or subtle and unilateral or bilateral. Dear Editor, A 26-year-old female with intermittent numbness and tingling in both hands later developed symptoms of migraine with visual aura in September 2019. They reported reduced fractional anisotropy in the genu of corpus callosum and prefrontal areas of the brain in patients with SS; but reduced fractional anisotropy in the body, rostrum and splenium of the corpus callosum in MS patients.11, There are several differential diagnoses for SS, and the most common are demyelinating processes like MS and ADEM; that is because of their autoimmune nature and similarities on MRI and clinical presentations; but hearing loss is a rare finding in MS, and retinal artery involvement in MS is peripheral retinal arteriolar vasculitis with cellular infiltration of the peripheral vitreous.5,15,22 There has been only one case of SS reported from Iran, who had first been diagnosed as MS because of her symptoms (paresthesia of four limbs) and MRI findings (multiple T2 and FLAIR high signal intensity lesions in periventricular areas); it was only after occurrence of hearing loss and tinnitus that the diagnosis of SS was suspected, and then confirmed by finding BRAO on ophthalmologic exam.13, There are some distinguishing features that help us to differentiate SS from MS and ADEM; (1) Corpus callosum involvement in SS is typically in the central portion of the corpus callosum and the periphery is spared, but in MS and ADEM the undersurface and septal interface of corpus callosum are involved. It was the initial presenting feature in our patient and has been described in a few cases [6]. NeuroBehcet disease with corpus callosum involvement. (Fig.2A)2A) and in the infratemporal artery in 3 cases. Susac's Syndrome | Cedars-Sinai Dear Editor , A 26-year-old female with intermittent numbness and tingling in both hands later developed symptoms of migraine with visual aura in September 2019. The endothelial barriers of the retina and cochlea are analogue to that of blood brain barrier, and these similarities can explain predilection of brain, retinal, and cochlear involvement in SS.6,7,18 Presence of anti-endothelial cell antibodies in some case reports is in favor of this immunologic pathophysiology, but it is not clear that these antibodies are the cause, or are produced secondarily. Testing is to evaluate your hearing wellness, which may include selling and fitting hearing aids. Susac's syndrome, a rare, potentially severe or lethal neurological disease. Retinal fluorescein angiography of patient number 3. 9] We believe that diagnosis could be arrived at earlier by applying our proposed classification system. There was more than one occlusion in 6 cases. Deane KD, Tyler KN, Johnson DW, Tanabe JL, Oskarrson BE, Nitka EE, et al. Susac Syndrome: an uncommon cause of impaired vision Demandez toujours l'avis d'un mdecin ou d'un autre professionnel de la sant qualifi pour toute question que vous pourriez avoir concernant une condition mdicale. Treatment of Susac syndrome with gamma globulin and corticosteroids. Advertisement intended for healthcare professionals. Some patients will develop epilepsy, dementia, and permanent vision or hearing loss as squela.8 therefore, early diagnosis and treatment is important to reduce the sequels.4,6,15,21 The sequels of encephalopathy occur in 60-70% of patients, but are mild in the majority of cases.9 In contrast to encephalopathy and vision loss that usually remit with no or mild sequels, SNHL in SS is severe and most often irreversible, and the patient may need hearing aid devices; cochlear implants may help in severe cases. As a library, NLM provides access to scientific literature. Federal government websites often end in .gov or .mil. However, all three features may not be present concurrently upon initial presentation. Susac Syndrome: What You Should Know | Anderson Audiology The site is secure. Susac syndrome - About the Disease - Genetic and Rare Diseases [1728] We therefore speculate that pregnancy might be a risk factor for disease flare-up. Ophthalmic examination revealed left superotemporal branch retinal artery occlusion, which was confirmed on Optical Coherence Tomography angiogram (Fig. Oligoclonal bands are positive in some case reports and negative in others.4,12-15,18,21,22,25, In SS may show a non-specific diffuse slowing pattern, without epileptiform discharge.4,12 EEG may also show multifocal cerebral dysfunction with intermittent bursts of irregular slow waves over both hemispheres, without epileptiform discharges.21, In SS with retinal arteriolar involvement may show segmental visual field defects on the basis of involved arterioles.4,21,25, The most popular pathophysiology of SS is an immune-mediated endotheliopthy.6,7 One of the supporting means of this theory is the presence of anti-endothelial cell antibodies in serum of SS patients; however, the diagnostic value of this antibody is not yet clear, because it may be present in some of the other autoimmune disorders like systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome and sarcoidosis.18, One of the most important differential diagnoses of SS is MS; as will be discussed later, this is due to similarities in clinical features and MRI findings.15 In a new study, Brandt et al. evaluated nine patients with SS by DTI and concluded that a 25% reduction of fractional anisotropy in the corpus callosum of their patients, especially of the genu, is a characteristic finding for SS. document.getElementById( "ak_js_1" ).setAttribute( "value", ( new Date() ).getTime() ); 2023 Anderson Audiology. memory impairment, confusion, behavioral disturbances, ataxia, dysarthria, paranoid psychosis, and headaches 1-8, sensorineural hearing loss at low and medium frequencies 1-8, branch retinal artery occlusions (BRAOs) leading to scotomata and vision distortion 1-8, which should be sought by fluorescein angiography 16. Susac's syndrome - Autoimmune Association Females are often affected (female:male ratio of 3:1), and the syndrome commonly occurs within the second to fourth decade of life [2, 3]. Approximately three females are affected for every male case 1. Rennebohm RM, Susac JO. It is characterized by a triad of encephalopathy, branch retinal artery occlusion and inner ear disease, notably hearing loss. The range of the differential diagnosis is wide, and it includes demyelinating diseases (e.g., multiple sclerosis, acute disseminated encephalomyelitis), autoimmune diseases (e.g., lupus erythematosus, neuro-Behet disease) and vascular occlusion (such as from an embolus or atherosclerosis). Susac syndrome symptoms overlap with various rheumatic diseases; awareness is crucial for prompt Multidisciplinary team collaboration. Fox RJ, Costello F, Judkins AR, Galetta SL, Maguire AM, Leonard B, et al. {"url":"/signup-modal-props.json?lang=us"}, Weerakkody Y, Gaillard F, Sharma R, et al. Early Hearing Loss Detection and Prevention, Hearing Aid Fitting Process: What To Expect, Rechargeable vs. AJR Am J Roentgenol. Ophthalmic manifestations may be the sole presenting sign of SS. Susac syndrome (SuS) is a rare disorder that is thought to be caused by autoimmune-mediated occlusions of microvessels in the brain, retina and inner ear [] which lead to a characteristic clinical triad of central nervous system (CNS) dysfunction, visual disturbances and hearing deficits [1-5].Typical findings in patients with SuS include branch retinal artery occlusions (BRAO) detectable on . Many patients also show psychiatric symptoms like behavior changes or paranoia. Future multicenter prospective studies are needed for better understanding of the syndrome, validation of the proposed classification, and effective planning of treatment strategy. The first symptom to appear is often repeated headaches, sometimes severe enough to feel like migraines. Because of its rarity and some similarities to other common neurological conditions such as multiple sclerosis and acute disseminated encephalomyelitis, it is often misdiagnosed and therefore mistreated. - A brief review of articles. Her cerebrospinal fluid protein was 0.32 g/l (normal range: 0.150.45 g/l) with glucose of 3.8 mmol/l (normal range: 2.23.9 mmol/l). [4] The encephalopathy is manifested by headache, motor deficiencies, sensor deficiencies, aphasia, cognitive impairment, and urinary insufficiency. Susac Syndrome - PMC - National Center for Biotechnology Information Rennebohm RM, Egan RA, Susac JO. 3. Symptoms and Causes What are the symptoms of Susac syndrome? Two patients had a low frequency sensorineural hearing loss. Patterns of retinal damage facilitate differential diagnosis between Susac syndrome and MS, Encephalopathy, visual disturbance and hearing loss-recognizing the symptoms of Susac syndrome, Characteristics of Susac syndrome: a review of all reported cases, Detection of branch retinal artery occlusions in Susac's syndrome, Progression of retinal artery occlusion from one eye to the other seems to be a characteristic finding in Susac syndrome, A case of isolated Susac occlusive retinal vasculitis, Susac syndrome: microangiopathy of the retina, cochlea and brain, Clinical, paraclinical and serological findings in Susac syndrome: an international multicenter study, Susac's syndromepathogenesis, clinical variants and treatment approaches. Finally, slower tapering (2.5 mg every month) should be considered. Susac syndrome is an autoimmune condition that affects the very small blood vessels in the brain, retina, and inner ear (cochlea). Joe SG, Kim JG, Kwon SU, Lee CW, Lim HW, Yoon YH. Audiology examination showed a right-side sensorineural hearing loss at low frequency in her right ear (40 dB at 250 Hz) and normal findings in her left ear (Fig. Difficulty thinking, including: confusion, short-term memory loss, reduced ability to problem solve. Susac syndrome is a rare condition characterized by the clinical triad of central nervous system (CNS) dysfunction, sensorineural hearing impairment, and branch retinal artery occlusion (BRAO). Susac's Syndrome--update. Susac syndrome: clinical characteristics and treatment in 29 new cases. 18. SS is frequently misdiagnosed and probably underdiagnosed. These may include magnetic resonance imaging (MRI). Hardy TA, Garsia RJ, Halmagyi GM, Lewis SJ, Harrisberg B, Fulham MJ, et al. Susac's Syndrome--update. During this period, urinary incontinence and generalized seizure may happen.4,12-15, In many of the reported cases of SS, sudden SNHL in association with peripheral vertigo, nystagmus and tinnitus occur after the encephalopathic features.10,13,16,17 The low and medium frequency SNHL occurs as a complication of cochlear apex arteriolar microinfarctions, may be permanent, and if severe, needs cochlear implantation.18, The third common clinical presentation of SS is BRAO, which means occlusion of some branches of the retinal artery due to endothelial injury. 2005;184 (5): 1688-90. The outcome of each patient is summarized in Table Table22. She has made good improvement and is currently on MMF 1 g twice daily and low-dose prednisolone, with stabilization and no further worsening of her symptoms. Saux A, Niango G, Charif M, Morales R, Mura F, Bonafe A, et al. Cerebrospinal fluid examination often shows a high protein level, with presence of oligoclonal band. Susac syndrome. One of the major presentations of SS is brain involvement, and MRI is the neuroimaging tool of choice in this syndrome.9, As mentioned earlier, one of the most common presentations of SS is microinfarctions in the brain that involves both white and grey matter.15 These microinfarctions can cause T2 hyperintense lesions at any area of the brain, including periventricular and juxtacortical areas, subcortical white matter (Figure 1A), cerebellum and corpus callosum;15,16 but microinfarctions in SS can also produce two specific findings on MRI: snowball lesions that represent microinfarctions of the central part of the corpus callosum, best seen on sagittal T2 and Fluid-attenuated inversion recovery (FLAIR) views (Figure 1B); and string of pearls that represents micro-infarctions of the internal capsule, best seen on diffusion weighted image sequences.17,18 Rennebohm et al. 12. The https:// ensures that you are connecting to the Clinical manifestations during the disease of Susac syndrome patients. Together with our communities, we pledge to do everything we can to ensure you have a safe visit as we honor our mission to help people hear better. 79 (3): 211-2. Susac Syndrome|Causes|Symptoms|Treatment|Diagnosis - Epainassist Susac syndrome affects women in almost 80% of cases [4] with symptoms starting in 4 out of 5 cases between 16 and 40 years-old with a mean age of onset estimated at 31.6 (10.4) years. Immunosuppression should be started as soon as possible and not be tapered very quickly.17 Kleffner et al. Saw VP, Canty PA, Green CM, Briggs RJ, Cremer PD, Harrisberg B, et al. Data are available upon reasonable request by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). 5. Fractional anisotropy reflects the spatial directionality of water diffusion that in microstructural damage of white matter decreases from normal values; this cannot be seen on conventional MRI. Le contenu de ce site Web est titre informatif uniquement et ne constitue pas un avis mdical. Curr. The data recorded for all Susac syndrome patients treated at the Sheba Medical Center between 1998 and 2014 included demographics, clinical signs at presentation and during the disease course, imaging findings, treatment, and prognosis. Susac Syndrome - Treatment and Symptoms - Autoimmune Sisters Susac Syndrome is a rare autoimmune disease in which the immune system attacks the smallest blood vessels in the brain, retina and inner ear. Treatment of Susac's Syndrome. Susac Syndrome is a rare autoimmune disease in which the immune system attacks the smallest blood vessels in the brain, retina and inner ear. Both eyes were involved in 3 cases, and only the right eye was involved in 7 cases. Some people with SuS also have ringing in the ears, dizziness or hearing loss ranging from mild to severe, which often appears as one of the first symptoms. government site. An MRI can reveal changes in your brain caused by Susac syndrome. A 'string of pearls' appearance due to punctate microinfarcts involving the internal capsule has been described 17. Journal of the neurological sciences. Susac syndrome: an organ-specific autoimmune endotheliopathy syndrome associated with anti-endothelial cell antibodies. Susac's Syndrome--update. They concluded that OCT is a useful diagnostic tool for differentiating SS from MS in challenging cases.26, A new neuroimaging modality used for assessment of nerve fiber integrity of the white matter is DTI. Anti-endothelial cell antibodies (AECAs) have been reported as being a promising marker in some studies, but these are not yet considered to be specific to the syndrome 10. Susac JO. Susac syndrome: clinical characteristics, clinical classification, and Sagittal T2 showing multiple large central callosal snowballs (B) (courtesy of Dr. Sahraian MA), The most common differential diagnoses of SS are MS and ADEM, but there are some distinguishing features as follows: (1) Corpus callosum involvement in SS is typically in the central portion of the corpus callosum and the periphery is spared, but in MS and ADEM the undersurface and septal interface of corpus callosum are involved. Mood problems, including depression, anxiety, anger, and aggression Psychosis, including delusions and hallucinations The Anatomy of the Brain Eye symptoms can include: Visual disturbances described as a dark shade or curtains over part of the vision Loss of peripheral (side) vision Inner ear symptoms may include: BRAO can lead to the person noticing a dark spot in a portion of their vision, due to injury to the retina of the eye as a result of reduced blood flow. 2] or retinopathy, encephalopathy, and deafness microangiopathy (RED-M) syndrome. The exam will include a fluorescein angiography, which measures the blood flow through the retina. (source). For full access to this pdf, sign in to an existing account, or purchase an annual subscription. She experienced recurrent severe episodes of vertigo, nausea, vomiting associated with ataxic gait and horizontal nystagmus. Susacs syndrome (SS) is a clinical triad of encephalopathy, branch retinal artery occlusion and sensorineural hearing loss and maybe due to an immune-mediated endotheliopathy. (Fig.1).1). It is characterised by the presence of encephalopathy, retinal vaso-occlusive disease and hearing loss. Susac's syndrome: the triad of microangiopathy of the brain and retina with hearing loss in young women. 1979;29 (3): 313-6. Other symptoms include recurrent headaches, dysarthria, memory impairment, confusion, personality/behavioural disturbances, tinnitus, sensorineural hearing loss and visual loss, with development of dark spots. Proposed classification of Susac syndrome. Susac syndrome (SuS) is a rare immune-mediated endotheliopathy that affects the small arterioles of the brain, retina and inner ear. Susac JO, Egan RA, Rennebohm RM, Lubow M. Susac's syndrome: 1975-2005 microangiopathy/autoimmune endotheliopathy.
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