Sneddon's Syndrome Research Articles

A NOTCH3 homozygous nonsense mutation in familial Sneddon syndrome with pediatric stroke

Sneddon syndrome is a rare disorder affecting small and medium-sized blood vessels that is characterized by the association of livedo reticularis and stroke. We performed whole-exome sequencing (WES) in 2 affected siblings of a consanguineous family with childhood-onset stroke and identified a homozygous nonsense mutation within the epidermal growth factor repeat (EGFr) 19 of NOTCH3, p.(Arg735Ter). WES of 6 additional cases with adult-onset stroke revealed 2 patients carrying heterozygous loss-of-function variants in putative NOTCH3 downstream genes, ANGPTL4, and PALLD. Our findings suggest that impaired NOTCH3 signaling is one underlying disease mechanism and that bi-allelic loss-of-function mutation in NOTCH3 is a cause of familial Sneddon syndrome with pediatric stroke.

Superficial Siderosis and Microbleed Restricted in Cortex Might Be Correlated to Atrophy and Cognitive Decline in Sneddon's Syndrome.

Objective: Sneddon's syndrome is a rare non-inflammatory arteriopathy affecting small and medium-sized arteries, characterized by a generalized livedo reticularis and recurrent transient ischemic attack or ischemic stroke. Hemorrhagic stroke was reported in limited cases, but microbleeds and superficial siderosis were rarely issued. We aimed to investigate the hemorrhagic imaging features of Sneddon's syndrome and explore the possible mechanism and clinical relevance.Methods: Clinical data and cerebral MR imaging including T2* sequence of seven consecutive patients with Sneddon's syndrome were reviewed.Results: The most common neurological manifestations were cognitive impairment and stroke attack (71.4%), followed by seizures and movement disorder (28.6%). Cerebral microbleeds were detected in six patients on T2* sequence, all of them presented with cortical microbleeds, only one of them with microbleeds in basal ganglion. More than five microbleeds were observed in four of these six patients. The majority of the microbleeds were predominantly cortical restricted and especially located in the cortical watersheds. Multiple superficial siderosis were identified mainly involving cortical watersheds in five cases. Significant cerebral atrophy with prominent secondary white matter hyperintensities in bilateral cortical watersheds were also observed. Abnormal tortuous and multiple focal occlusion of bilateral distal MCA were shown in one patient by DSA. No stenosis of proximal segment of cerebral arteries was detected in all the patients.Conclusions: This is the first report illustrating abundant cortical microbleeds and superficial siderosis mainly involved the anterior and posterior cortical watersheds in Sneddon's syndrome. The surprisingly identical topographic distribution of hemorrhagic lesions and the obvious atrophy suggest cerebral atrophy might be secondary to the microangiopathy related hemorrhagic lesions and further contribute to the neurological deficit, especially the early cognitive decline in Sneddon syndrome.

CNS vasculopathies: Challenging mimickers of primary angiitis of the central nervous system.

Primary angiitis of the central nervous system (CNS) is an inflammatory vasculopathy affecting the brain and spinal cord. It is a difficult diagnosis to make because of its insidious nonspecific course and its multiple mimics. This review identifies and discusses some noninfectious mimickers of primary CNS angiitis, including: reversible cerebral vasoconstriction syndrome, Sneddon's Syndrome, amyloid-beta-related angiopathy, Susac Syndrome, and neurosarcoidosis. Each condition will be reviewed in terms of epidemiology, pathology, clinical presentation, diagnostic approach, and treatment. Distinguishing these mimics from the primary angiitis of the CNS is important for proper treatment and prognosis.

Sneddon’s Syndrome: clinical case

We report a 40-year-old female. The high blood pressure was found in Family history, hospitalized in neurology for recurrent ischemic stroke so the etiological assessment was negative, opinion was sought for lesions of livedo at the level of the members back to 2 years without the concept of miscarriage or Raynaud’s phenomenon, neither photosensitivity nor a dry syndrome. Dermatologic examination showed dusky erythematous to violaceous, irregular, broken circular segments, resulting in a seemingly larger pattern, located on limbs, trunk, and buttocks, exaggerated by the cold and persistent on warming. A report looking for the antiphospholipid antibodies syndrome was positive and the skin biopsy was in favor of a Sneddon syndrome. The patient was treated by anticoagulants and antiplatelet agents with good evolution.

Abstract WP476: Remarkable Hemorrhagic Imaging Manifestations Might Be Responsible for the Prominent Atrophy and Cognitive Decline in Sneddon Syndrome

Objective: Sneddon syndrome is a rare non-inflammatory arteriopathy affecting small and medium-sized arteries, characterized by a generalized livedo reticularis and recurrent ischemic stroke. Hemorrhagic stroke was reported in limited cases, but microbleeds and superficial siderosis were rarely issued, which might be underdiagnosed due to the limitation of technique. We aimed to investigate the hemorrhagic imaging features of Sneddon syndrome and explore the possible mechanism and clinical relevance. Methods: Clinical data and cerebral MR imaging including T2* sequence of 6 consecutive patients with Sneddon syndrome were reviewed. Results: The most common neurological manifestations were cognitive impairment and stroke attack(66.7%), followed by seizures(33.3%) and movement disorder(16.7%). Cerebral microbleeds were detected in all the patients on T2* sequence,four of whom presented more than 5 microbleeds.The majority of the microbleeds were predominantly cortical restricted and especially located in the cortical watersheds. Multiple superficial siderosis were identified and mainly involved cortical watersheds in 5 cases. Significant cerebral atrophy with prominent secondary white matter hyperintensities in bilateral cortical watersheds were also observed. Abnormal tortuous and multiple focal occlusion of bilateral distal MCA were shown in 1 patient by DSA. No stenosis of proximal segment of cerebral arteries was detected in all the patients. Conclusions: This is the first report illustrating abundant cortical microbleeds and superficial siderosis mainly involved the anterior and posterior cortical watersheds in Sneddon syndrome. The surprisingly identical topographic distribution of hemorrhagic lesions and the corresponding obvious atrophy suggest cerebral atrophy might be secondary to the microangiopathy related hemorrhagic lesions and further contribute to the neurological deficit, especially the early cognitive decline in Sneddon syndrome,although further investigation is needed to elucidate the precise underlying pathogenesis. These highlight cortical microbleeds and superficial siderosis located in cortical watershed and the secondary atrophy in youth might be highly indicative of Sneddon syndrome.

Sneddon syndrome: anaesthetic and surgical challenges in cardiac valve surgery.

Sneddon syndrome: anaesthetic and surgical challenges in cardiac valve surgery.

Echocardiographic features in antiphospholipid-negative Sneddon's syndrome and potential association with severity of neurological symptoms or recurrence of strokes: a longitudinal cohort study.

Sneddon's syndrome (SS) may be classified as antiphospholipid positive (aPL+) or negative (aPL- SS). An association between Libman-Sacks (LS) endocarditis and strokes has been described in aPL+ patients. To describe cardiac involvement in aPL- SS and assess the potential association between LS endocarditis and severity or recurrence of neurological symptoms. This longitudinal cohort study included aPL- SS patients followed in our departments between 1991 and June 2018. All patients underwent transthoracic 2D and Doppler echocardiography at diagnosis. Follow-up echocardiography was performed annually and the potential relationship between LS endocarditis development and neurovascular relapse as well as long-term cardiac worsening was prospectively assessed. We included 61 patients [52 women; median age 45 (range 24-60)]. For valvular involvement, 36 (59%) patients showed leaflet thickening; 18 (29.5%) had LS endocarditis at baseline. During a median follow-up of 72 months, LS endocarditis developed in eight (17.4%) patients, and 13 (28.3%) showed significant worsening of their cardiac status, including two who needed valvular replacement. After adjusting for baseline antithrombotic treatment regimen, neither the presence of LS endocarditis at baseline nor development during follow-up was associated with neurological relapse [hazard ratio (HR): 1.06, 95% confidence interval (CI): 0.33-4.74, P = 0.92] and [HR: 0.38, 95% CI: 0.02-1.89, P = 0.31], respectively. A long-term follow-up is needed to detect cardiac complications in aPL- SS. No change in neurological relapse was observed in patients presenting LS endocarditis occurrence during follow-up without any modification in antithrombotic treatment. Further research is necessary to assess the usefulness of treatment escalation in these patients.

WED 253 An atypical presentation of sneddon syndrome

A 50-year-old female was admitted following a subacute and increasing headache, numbness in both hands and feet, generalised weakness and confusion.An MRI brain revealed an acute left temporal infarct with multi-focal established infarcts. MR angiography demonstrated marked occlusive disease affecting terminal internal carotid artery and both middle cerebral and posterior cerebral arteries, in a potential Moyamoya pattern.Lumbar puncture, extensive blood tests and echocardiography were unremarkable. A skin biopsy showed intimal thickening of the deep dermal arteries compatible with a diagnosis of Sneddon Syndrome. Livedo reticularis was absent and antiphospholipid antibodies negative. Antiplatelet therapy only was commenced given her seronegativity and Moyamoya.DiscussionSneddon syndrome is an uncommon disorder, characterised as generalised livedo reticularis with stroke (Sneddon, 1965). It is an increasingly recognised cause of ischaemic stroke in young adults, however, its clinical course remains poorly defined in the literature (Boesch et al. 2003). It is increasingly associated with Moyamoya syndrome, posing a challenge in terms of anticoagulation in these patients (Fierini et al. 2015). To our knowledge, this is only the second reported case without livedo reticularis (Marianetti et al. 2011) - highlighting the importance of skin biopsy - and the first with this clinical and radiological combination.

AVE isquêmico em paciente jovem sem fatores de risco: relato de caso

Acidente vascular encefálico (AVE) caracteriza-se por um complexo de sintomas decorrentes de alterações no suporte sanguíneo cerebral, que duram pelo menos 24 horas causam lesões cerebrais. Pode ser classificado em isquêmico (AVEi) e hemorrágico (AVEh), sendo que o mais comum deles é o AVEi, caracterizado por interrupção do fluxo sanguíneo em uma determinada área do encéfalo devido a obstrução arterial ou venosa. A falta de suprimento sanguíneo causa um infarto na área vascularizada pelo vaso obstruído, causando morte neuronal. Existem fatores de risco modificáveis e não modificáveis para o AVE, sendo alguns deles: hipertensão, diabetes, tabagismo, etilismo, sedentarismo, dislipidemias, idade superior aos 55 anos, raça negra, história familiar e AVE prévio. O diagnóstico segue protocolos de acordo com o tempo de início dos sintomas, e basicamente, avalia-se quadro clínico, TC de crânio sem contraste ou ressonância magnética de crânio e exames laboratoriais. O tratamento varia de acordo com sua classificação. No caso apresentado a paciente do sexo feminino, sem comorbidades prévias e fatores de risco, desenvolveu um AVEi mesencefálico com graves sequelas. Não foram investigados alterações em genes da coagulação que pudessem explicar a causa da patologia. O AVEi jovem consiste no acidente vascular encefálico presente em adultos com menos de 45 anos. A patologia necessita, além das investigações padrões, de uma averiguação quanto a etiologia genética. Várias patologias estão associadas ao quadro, como CADASIL, doença de Fraby, coagulopatias, anemia de células falciformes, síndrome de Sneddon, MELAS, síndrome de Ehlers-Danlos tipo IV, neurofibrimatose tipo 1 e doença de Moya-Moya. Diante disso evidencia-se a necessidade de se conhecer sobre novos estudos e atualizações que descrevam causas não tão conhecidas de AVE.

Les endocardites non infectieuses

Non-infective endocarditis, also referred to as non-bacterial thrombotic endocarditis, represent a wide range of rare pathologies, often severe. This review gathered the data available in the literature, to decipher the major information collected on the pathophysiology, the diagnosis and the treatment of these heterogeneous diseases, often misdiagnosed. Characteristics of non-infective endocarditis are similar to infective endocarditis in terms of valvular lesions (mostly left-sided, with regurgitations and vegetations), and their complications (embolism). The diagnosis of non-infective endocarditis is usually considered in patients with blood culture-negative endocarditis. Beyond the usual suspects – marastic endocarditis and systemic lupus erythematosus – which represent more than 75% of the cases, Behçet disease and hypereosinophilic syndrome are the main causes of non-infective endocarditis. More seldomly, rheumatoid arthritis, adult-onset Still disease, allergy to pork in patients with valvular procine bioprosthesis, systemic scleroderma, Cogan or Sneddon syndrome should be suspected. Diagnostic approach is based on history and physical examination, with a special focus on extra-cardiac manifestations, as well as echocardiography, and computed tomography. Treatment relies on intensive management of the underlying disease. Curative anticoagulation is often necessary. Although indications for cardiac surgery are poorly defined, as compared to infective endocarditis, data currently available suggest that an optimal control of the underlying disease before cardiac surgery is of utmost importance, as it dramatically reduces the risk of postoperative complications.

OP-434 - Aortic and Mitral Valvular Involvement and Serious Coronary Artery Disease Associated with Sneddon Syndrome

OP-434 - Aortic and Mitral Valvular Involvement and Serious Coronary Artery Disease Associated with Sneddon Syndrome

Sneddon's syndrome presented at first with Hemorrhagic stroke: A case report

Sneddon's syndrome presented at first with Hemorrhagic stroke: A case report

Sneddon Syndrome with the Initial Presentation of Intracranial Hemorrhage: A Case Report

Sneddon syndrome (SS) is characterized by chronic, progressive arteriopathy, which causes ischemic stroke and skin lesions. It seems that thrombotic or embolic processes in the vessels may be involved in the pathology of this syndrome. Neurological symptoms always occur due to the ischemic events of the cerebrovascular system, and the associated cutaneous manifestations include deep blue skin lesions with irregular margins, known as livedo reticularis and livedo racemosa. Despite the ischemic events, hemorrhagic cerebral accidents are unusual in SS. Our case was apparently a normal woman with negative medical history who, despite the normal ischemic cerebral manifestations, initially presented with intracranial hemorrhage, which progressed to new skin lesions (livedo reticularis) after a few days. In the follow-up, the patient was diagnosed with SS.

Vasculopathies, cutaneous necrosis and emergency in dermatology.

Most emergencies in dermatology comprise a variety of entities with a usually benign course. However, vasculopathies and vasculitis are not common, but they could represent respectively 1.9% and 4.4% of these entities according to some studies of Emergency Dermatology Department. They become an important disease which has to be identified early to establish appropriate management and treatment. Some of them are well known, such as the leukocitoclastic vasculitis, Schölein-Henoch, panarteritis nodosa, antineutrophil cytoplasmic antibody associated vasculitis, giant cell arteritis, cryoglobulinemic vasculitis and antiphospholipid syndrome. More frequent vasculopathies are livedoid vasculopathy, pigmented purpuric dermatosis and calciphylaxis. Less common ones are caused by interferon and cholesterol crystal embolization. Others are very infrequent as Degos disease and Sneddon Syndrome. Among the more recently described ones there are deficiency of adenosine deaminase type 2 and crystalglobulinemia. The other group is composed of vasculopathies associated to microorganism as infective endocarditis, septic vasculopathy, aspergillosis, fusariosis, strongiloidosis, ecthyma gangrenosum, lucio phenomenon of leprosy and necrotic arachnidism. Finally, among these entities we can also find diseases associated with proinflammatory stages as disseminated intravascular coagulation, myeloproliferative disorders, intravascular lymphoma, metastasis intravascular. When we face cutaneous lesions characterized by reticulated violaceous lesions, palpable purpura or cutaneous necrosis, a careful clinico-pathological correlation as well as some laboratory or radiological tests are mandatory to further delineate a diagnosis and a proper first line empirical treatment.

Sneddon syndrome associated with antiphospholipid syndrome: Clinical descriptions and a literature review

Abstract Sneddon syndrome is a rare non-inflammatory obliterative vasculopathy, characterized by the association of cardiovascular (arterial hypertension, intermittent claudication, and coronary artery disease) and neurological events (ischemic stroke, headache, dizziness and convulsions), and livedo reticularis/livedo racemosa. The case is presented of a woman admitted with an ischemic neurological disease, hypertension, vascular problems, and skin lesions. The skin biopsy was classified as surface perivascular lymphocytic dermatitis, suggestive of occlusive lesion.

Treatment of Skin Ulcers Secondary to Sneddon Syndrome With Alprostadil (Prostaglandin E1).

Treatment of Skin Ulcers Secondary to Sneddon Syndrome With Alprostadil (Prostaglandin E1).

Sneddon's syndrome: it is all in the ectoderm

A 51-year-old man gave a 2-year history of worsening mobility, cognitive decline and headaches. He had a history of thromboembolic stroke, recurrent transient ischaemic attacks and a spontaneous intraventricular haemorrhage....

The diagnostic challenge of Divry van Bogaert and Sneddon Syndrome: Report of three cases and literature review

Divry van Bogaert Syndrome (DBS) is a familial juvenile-onset disorder characterized by livedo racemosa, white matter disease, dementia, epilepsy and angiographic finding of “cerebral angiomatosis”. A similar syndrome including livedo racemosa and cerebrovascular disease, often associated with anticardiolipin antibodies, has been described as Sneddon Syndrome (SS) highlighting the question whether these two conditions have to be considered different entities or indeed different features of a unique syndrome. Herein, we report the clinical, neuroradiological, histopathological findings and follow up of three cases diagnosed as Divry-van Bogaert Syndrome, including an updated review of literature of both DBS and SS cases. Our findings support the assumption that DBS and SS are different disease entities. DBS is characterized by the typical angiographic feature of angiomatosis, a hereditary trait and a juvenile onset of cognitive impairment and leukoaraiosis, whereas SS has less severe manifestations of cerebrovascular disease associated with livedo racemosa but without the characteristic cerebral angiography. The report of our cases and the literature review underline the necessity of a detailed work-up and the collection of larger series to better clarify the DBS and SS phenotype and course.

Ian Bruce Sneddon (1915-1987).

Ian Bruce Sneddon (1915-1987).

Cardiac manifestations of Sneddon's syndrome

Cardiac manifestations of Sneddon's syndrome