Susac syndrome is an immune-mediated, pauci-inflammatory, ischemia-producing, occlusive microvascular endotheliopathy/basement membranopathy that affects the brain, retina, and inner ear. Treatment ...of Susac syndrome is particularly challenging. The organs involved can easily become irreversibly damaged, and the window of opportunity to protect them is often short. Optimal outcome requires rapid and complete disease suppression. Adding to the challenge is the absence of objective biomarkers of disease activity and the great variability in presentation, timing and extent of peak severity, duration of peak severity, and natural disease course. There have been no randomized controlled trials or prospective treatment studies. We offer treatment guidelines based on cumulative clinical experience and a large cohort of patients followed longitudinally in a comprehensive database project. These guidelines state our preferences but do allow flexibility and discuss other options. The guidelines also serve as an initial step in the planning of prospective treatment studies, future consensus-based recommendations, and future randomized controlled trials.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Interindividual gene copy-number variation (CNV) of complement component
C4 and its associated polymorphisms in gene size (long and short) and protein isotypes (C4A and C4B) probably lead to ...different susceptibilities to autoimmune disease. We investigated the
C4 gene CNV in 1,241 European Americans, including patients with systemic lupus erythematosus (SLE), their first-degree relatives, and unrelated healthy subjects, by definitive genotyping and phenotyping techniques. The gene copy number (GCN) varied from 2 to 6 for total
C4, from 0 to 5 for
C4A, and from 0 to 4 for
C4B. Four copies of total
C4, two copies of
C4A, and two copies of
C4B were the most common GCN counts, but each constituted only between one-half and three-quarters of the study populations. Long
C4 genes were strongly correlated with
C4A (
R=0.695;
P<.0001). Short
C4 genes were correlated with
C4B (
R=0.437;
P<.0001). In comparison with healthy subjects, patients with SLE clearly had the GCN of total
C4 and
C4A shifting to the lower side. The risk of SLE disease susceptibility significantly increased among subjects with only two copies of total
C4 (patients 9.3%; unrelated controls 1.5%; odds ratio OR = 6.514;
P=.00002) but decreased in those with ≥5 copies of
C4 (patients 5.79%; controls 12%; OR=0.466;
P=.016). Both zero copies (OR=5.267;
P=.001) and one copy (OR=1.613;
P=.022) of
C4A were risk factors for SLE, whereas ≥3 copies of
C4A appeared to be protective (OR=0.574;
P=.012). Family-based association tests suggested that a specific haplotype with a single short
C4B in tight linkage disequilibrium with the −308A allele of
TNFA was more likely to be transmitted to patients with SLE. This work demonstrates how gene CNV and its related polymorphisms are associated with the susceptibility to a human complex disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
A 24-year-old woman developed encephalopathy, branch retinal artery occlusion, hearing loss, and had “snowball” lesions in the corpus callosum, classic findings of Susac syndrome (SuS). ...Despite intensive immunosuppressive therapy, she lapsed into a coma, and died 7 months after the onset of her illness. Neuropathological examination, revealed perivascular inflammation and vasculitis involving small vessels, associated with vascular narrowing and occlusion, and numerous microinfarcts diffusely throughout the brain. The findings establish SuS as a neuroinflammatory condition that can include vasculitis. This represents the most comprehensive report of the neuropathological findings in SuS.
Objective
Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin‐1 (IL‐1) and IL‐6 inhibitors appear to be effective treatments. Pulmonary ...arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients.
Methods
Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.
Results
The patients (n = 25) were significantly (P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL‐1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68%) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti–IL‐1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2 months from the diagnosis of pulmonary complications.
Conclusion
PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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.
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.
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Susac's syndrome (SS) consists of the clinical triad of encephalopathy, branch retinal artery occlusions (BRAO) and hearing loss. It is due to a microangiopathy affecting the precapillary ...arterioles of the brain, retina, and inner ear (cochlea and semicircular canals). Women are more commonly affected than men (3:1); the age of onset ranges from 9 to 58 years; but young women between the ages of 20 and 40 are most vulnerable. The encephalopathy is almost always accompanied by headache which may be the presenting feature. Multifocal neurological signs and symptoms, psychiatric disturbances, cognitive changes, memory loss, and confusion may rapidly progress to dementia. The MRI shows a distinctive white matter disturbance that always affects the corpus callosum. The central callosal fibers are particularly vulnerable and central callosal holes develop as the active lesions resolve. Linear defects (spokes) and rather large round lesions (snowballs) sometime dominate the MRI findings, which include cortical, deep gray (70%) and leptomeningeal involvement (33%). Frequently, the lesions enhance and may be evident on diffusion weighted imaging (DWI). The BRAO are best evaluated with fluorescein angiography, which may show the pathognomonic multifocal fluorescence. Gass plaques are frequently present and reflect endothelial damage. Brain biopsy shows microinfarction to be the basic pathology, but more recent pathological studies have shown endothelial changes that are typical for an antiendothelial cell injury syndrome. Elevated levels of Factor VIII and von Willebrand Factor Antigen reflect the endothelial perturbation. Despite extensive evaluations, a procoagulant state has never been demonstrated. SS is an autoimmune endotheliopathy that requires treatment with immunosuppressants: steroids, cyclophosphamide, and intravenous immunoglobulin, usually in combination. Aspirin is a useful adjunct.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In the era of the COVID-19 pandemic, medical professionals and broader community are being heavily pushed to vaccinate against COVID. In many cases, vaccination was mandatory, usually without proper ...informed consent. Many citizens questioned reasonableness of the mass vaccination campaign, especially vaccination of children, and, accordingly, asked to be exempted from the compulsory vaccination.
This document is aimed to exempt and protect children from vaccination against COVID, and is intended to inform everyone involved in making vaccination decisions. Not a single child should be given any of the COVID vaccines. Naturally acquired immunity against COVID significantly exceeds the immunity induced by vaccines. The interaction between the immune system and viruses is multidimensional and involves complex and delicate adjustments in both the virus and the immune system at the individual and population level. COVID vaccines use a simplified, one-dimensional, exclusionary approach that can disrupt important components and functions of the immune system. The mass vaccination campaign against COVID causes serious damage to the immune ecosystem, it is responsible for generation of a long series of new dominant variants that become more contagious and resistant to vaccines (due to the phenomenon of immune escape) and will inevitably become more virulent. This is based on the fundamental laws of natural selection and was predictable. The organizers of the mass vaccination campaign failed to assess the complexity and sensitivity of the immune ecosystem and, thus, prolonged the COVID-19 pandemic and made it catastrophically dangerous. COVID vaccines have proven unable to prevent infection or transmission of the virus. The virus, as expected, quickly became resistant to vaccine neutralizing antibodies.
For the above-mentioned scientific reasons, the mass vaccination campaign against COVID must be stopped for the whole of humanity and especially for children.
As a direct result of the mass vaccination campaign against COVID (in all age groups), humanity is likely to face a threatening situation that could potentially become catastrophic. The mass ...vaccination campaign has caused multiple increasingly contagious dominant variants of the SARS-CoV-2 virus.
The reason is the phenomenon of immune escape, neutralizing antibodies induced by the vaccine quickly cease their function, and vaccine non-neutralizing antibodies can make the virus more contagious a form of antibody-mediated or antibody dependent amplification of the infection.
Thus, anti-COVID vaccines do not teach the innate immune system to fight the virus, but instead non-neutralizing vaccine antibodies neutralize the innate immune system of those who are vaccinated. Vaccines against COVID do not contribute to the formation of collective immunity, but, on the contrary, make the virus more contagious. The mass vaccination campaign predisposes to depletion of immunity in vaccinated people. Vaccinated people (of all ages) are currently repeatedly re-infected with SARS-CoV-2. The depletion of immunity decreases a vaccinated persons ability to cope not only with SARS-CoV-2 but with other infections, including EBV, CMV, herpes virus and even tuberculosis. To solve the problem, it is necessary to put an end to simplistic and incorrect directives, to create conditions for a constructive dialogue between scientists and doctors who were responsible for the prevailing narrative about COVID and the policy of combating it, and those scientists and doctors who challenged the prevailing narrative and its policies. We must also encourage such dialogue among citizens dialogue and demystifying education that will improve understanding of the COVID situation, create consensus, and unite people in positive, constructive efforts to save lives and end this pandemic.
Objective
To use juvenile dermatomyositis (DM) survey data and expert opinion to develop a small number of consensus treatment protocols, which reflect current initial treatment of moderately severe ...juvenile DM.
Methods
A consensus meeting was held in Toronto, Ontario, Canada on December 1–2, 2007. Nominal group technique was used to achieve consensus on treatment protocols, which represented typical management of moderately severe juvenile DM. Consensus was also reached as to which patients these protocols would be applicable (inclusion and exclusion criteria), which initial investigations should be done prior to initiating one of these protocols, which data should be collected to evaluate these protocols, and the concomitant interventions required or recommended.
Results
Three protocols that described the first 2 months of treatment were developed. All protocols included corticosteroids and methotrexate. One protocol also included intravenous gamma globulin. Consensus was achieved for all issues that were addressed by conference participants, although there were some areas of controversy.
Conclusion
Despite considerable variation in clinical practice, it is possible to achieve consensus on the initial treatment of juvenile DM. Once these protocols are extended beyond 2 months, these protocols will be available for clinical use. By using methods that account for differences between patients (confounding by indication), the comparative effectiveness of the protocols will be evaluated. In the future, the goal will be to identify the optimal treatment of moderately severe juvenile DM.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Susac syndrome is a rare, immune-mediated disease characterized by encephalopathy, branch retinal artery occlusion, and hearing loss. Herein, we describe the electron microscopic findings of three ...brain biopsies and two brain autopsies performed on five patients whose working clinical diagnosis was Susac syndrome. In all five cases, the key findings were basement membrane thickening and collagen deposition in the perivascular space involving small vessels and leading to thickening of vessel walls, narrowing, and vascular occlusion. These findings indicate that Susac syndrome is a microvascular disease. Mononuclear cells were present in the perivascular space, underlining the inflammatory nature of the pathology. Though nonspecific, the changes can be distinguished from genetic and acquired small vessel diseases. The encephalopathy of Susac syndrome overlaps clinically with degenerative and infectious conditions, and brain biopsy may be used for its diagnosis. Its vascular etiology may not be obvious on light microscopy, and electron microscopy is important for its confirmation.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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