Sneddon syndrome and non-bacterial thrombotic endocarditis
Sneddon syndrome (SS) is a non-inflammatory thrombotic arteriopathy characterized by the combination of cerebrovascular disease and livedo racemosa (LR). Autopsy studies are scanty. We described the full clinico-pathological study of an SS patient with marantic endocarditis.
This right-handed patient was admitted in 1980, at age 53, with a 4-year history of progressive cognitive decline. There was generalized LR (Fig. 1A). She had 7 pregnancies all of them ending in spontaneous abortion. There was a grade II pansystolic murmur at the cardiac apex. Neurological examination showed disinhibition, moderate fluent dysphasia with paraphasias, oppositional paratonic rigidity, dysarthria, shuffling gait, and hypereflexia, both plantar responses being extensor. Extensive laboratory data, including luetic serology, coagulation profile with partial thromboplastin time, platelet function studies, antinuclear antibody, LE cell preparations, rheumatoid factor, cryoglobulins, total haemolytic complement, C3 and circulating immune complex, were normal or negative. ECG was normal. Figure 1B, C illustrates cranial angiographic findings. Cranial CT scan (not shown) revealed brain atrophy and a hypodense lesion in the right parieto-occipital area.
Two years later, she was readmitted with an acute, afebrile picture of distal limb ischemia that caused dry gangrene, the patient dying 8 days after admission.
Brain and general autopsy findings are illustrated in Figure 1D-O. We reviewed archived photographic and pathological material.
The brain weighed 855 g. Figure 1D-F shows macroscopic brain findings. Microscopic study revealed widespread non-inflammatory occlusion of large to medium-size arteries and arterioles (Fig. 1G-I). We found no evidence of either acute or chronic inflammation, fibrinoid necrosis or lipid deposits. Figure 1J illustrates hyperplasia of leptomeningeal vessels. Figure 1K shows histological appearance of the observed right occipital AVM. There were numerous subcortical and intracortical infarcts (Fig. 1L).
General autopsy showed non-bacterial thrombotic endocarditis of mitral and aortic valves (Fig. 1M), and a systemic arteriopathy involving all large to medium-size vessels examined with occasional presence of mural thrombi (Fig. 1N, O).
In this case the possibility of primary antiphospholipid-related SS cannot entirely be excluded given that, inevitably, at the time of admission blood tests did not screen anti-cardiolipin and anti-β2GPI antibodies. Nevertheless, the possibility of SLE was ruled out, and normal coagulation profile including partial thromboplastin time and platelet function study argues in favour of idiopathic SS.
Our autopsy study confirms that the pathological basis of SS is a systemic occlusive, non-inflammatory vasculopathy mainly involving large to medium-size arteries and arterioles. It was characterized by intimal hyperplasia with musculoelastic proliferation, which could in turn lead to recanalized thrombosis. The observed marantic endocarditis, for a long time subclinical till the final episode of systemic embolism, supports the notion that idiopathic SS is frequently associated with heart valvular lesions. Furthermore, such systemic occlusive arteriopathy concurs with the proposal that valvular heart disease does not influence the type of brain infarct, namely that ischemic strokes are caused by widespread cerebral arteriopathy.
Cerebral angiography showed occlusion of anterior and middle cerebral arteries with collateral circulation and anastomoses via perforating vessels at the base of the brain, which depicted a moyamoya pattern. Macroscopic brain appearance illustrated a profuse network of subarachnoid vessels, some of them being occluded arterioles. We interpret that such vascular network is due to profuse collateral circulation of the brain via transdural anastomoses and anastomoses between intracranial arteries, and not as being a primary meningeal angiomatosis. The observed association between brain AVM and SS has not previously been reported and might be incidental. Be that as it may, AVM or pseudoangiomatosis associated with moyamoya pattern might be pathogenic in SS cases presenting with intracranial hemorrhage.
University of Cantabria, Service of Neurology, University Hospital “Marqués de Valdecilla (IDIVAL)”,
“Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)”, Santander, Spain
Sneddon syndrome and non-bacterial thrombotic endocarditis: a clinicopathological study.
Berciano J, Terán-Villagrá N
J Neurol. 2018 Sep