Multiphasic disseminated encephalomyelitis, systemic lupus erythematosus and antiphospholipid syndrome

We report a case of multiphasic disseminated encephalomyelitis (MDEM) associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome. The initial presentation was suggestive of multiple sclerosis. Further clinical attacks, MRI imaging, and CSF findings led to a diagnosis of disseminated encephalomyelitis (DEM). Multiple episodes of neurological dysfunction, which differed in clinical presentation, further categorized the diagnosis as multiphasic DEM. The co-occurrence SLE and antiphospholipid syndrome is unusual and provided an additional diagnostic challenge.     

Primary antiphospholipid syndrome and neurologic events

The occurrence of lupus anticoagulant and anticardiolipin antibodies was demonstrated in a girl affected by recurrent episodes of visual disturbances, with ophthalmologic evidence of visual impairment and sometimes accompanied by migraine. Systemic lupus erythematosus was excluded on the basis of both clinical and serologic criteria and the diagnosis of primary antiphospholipid syndrome was made. Vascular pathogenesis was suggested by the characteristic symptoms. The serologic demonstration of antiphospholipid antibodies made it possible to relate the illness to an immune-mediated thrombotic tendency. This patient demonstrated that the diagnosis of primary antiphospholipid syndrome must always be considered in focal cerebral or retinal ischemia in childhood.     

An autopsy case of catastrophic antiphospholipid syndrome presenting with recurrent multiple cerebral infarction associated with lung cancer]

We reported an autopsy case of cerebral infarction with primary lung cancer. The patient was a 50-year-old man. Despite having been treated with warfarin potassium and ticlopidine hydrochloride, he relapsed cerebral infarction. His laboratory data on admission showed that lupus anticoagulant was positive, together with a high value of beta-thromboglobulin, thrombin-antithrombin III complex, markers of platelet and coagulation activation, CEA and CA 19-9. The autopsy finding revealed a primary papillary adenocarcinoma in the right lower lung, multiple cerebral infarction, renal infarction, pulmonary infarction and splenic infarction. The atherosclerotic changes were mild in the whole tissues and findings of vasculitis were not observed. Recurrence of cerebral infarction was effectively suppressed with the addition of steroid therapy to antithrombotic therapy. This case was considered as catastrophic antiphospholipid syndrome. It is necessary to differentiate antiphospholipid syndrome in case of the abnormal coagulation and fibrinolytic factors with recurrent cerebral infarction. Moreover, systemic examinations are important, because malignant tumor may exist on the background of the case.     

Claude's syndrome associated with supranuclear horizontal gaze palsy caused by dorsomedial midbrain infarction

Claude's syndrome caused by dorsal midbrain lesion is characterized by ipsilateral third nerve palsy and contralateral ataxia. To date, reports in the literature concerning Claude's syndrome associated with the midbrain paresis of horizontal gaze are rare. A 62-year-old man suddenly developed left third cranial nerve palsy, right lateral gaze palsy, and right ataxia. Intact Bell's phenomenon and preserved right horizontal oculocephalic reflex suggested the lateral gaze palsy in the right eye was supranuclear in nature. Magnetic resonance imaging (MRI) revealed an infarction in the left dorsomedial midbrain. Although the red nucleus has often been suggested as the lesion site responsible for Claude's syndrome, a lesion of the superior cerebellar peduncle just below and medial to the red nucleus could be responsible for this syndrome. This case demonstrates neurological heterogeneity of midbrain infarction.     

Chorea and high antiphospholipid antibodies: probable primary antiphospholipid syndrome

A young man presented with generalized chorea as the first manifestation of probable primary antiphospholipid syndrome. He was well till 3 months before admission when he started to have involuntary, choreiform movements involving all extremities, the head and the bulbar muscles. Apart from these movements his physical examination was otherwise unremarkable. Laboratory investigations revealed mild thrombocytopenia, high partial thromboplastin time (PTT) only partially corrected by the addition of normal plasma, false positive syphilis serology, weakly positive antinuclear antibody and a high level of IgG anticardiolipin antibodies. Brain magnetic resonance imaging (MRI) showed multiple scattered small areas of high signal intensity on T2 weighted image in the area of centrum semiovale bilaterally. The patient was started on aspirin and prednisone with rapid symptomatic improvement. Despite the difficulty in proving the association between chorea and the high antiphospholipid antibodies, chorea appears in this case to be the initial symptom of primary antiphospholipid syndrome and we suggest screening for antiphospholipid antibodies in unexplained cases of chorea.     

Chorea as the presenting clinical feature of primary antiphospholipid syndrome in childhood.

Three patients, aged five to 16 years, developed chorea as the only or main clinical manifestation of primary antiphospholipid syndrome. In two cases, complaints were self-limited five to eight months after onset. In one patient, the clinical course was complicated by valvulitis. Under corticosteroid treatment, chorea disappeared and cardiac involvement stabilised. Primary antiphospholipid syndrome is a probably under-recognised differential diagnosis of choreatic syndromes in childhood. Assessment of anticardiolipin antibodies and/or lupus anticoagulant should be an obligatory part of the diagnostic work-up of such patients. Early diagnosis of primary antiphospholipid syndrome may improve clinical management and prognosis.     

Antiphospholipid syndrome and dystonia-parkinsonism. A case report

Background: Although clinically evident and MRI confirmed, basal ganglia involvement, is usual in primary antiphospholipid syndrome, extrapyramidal disorders such as parkinsonism and dystonia are very rare. We were unable to find any report in the literature on dystonia-parkinsonism in patients with primary antiphospholipid syndrome. Here we report an adult patient with dystonia-parkinsonism and primary antiphospholipid syndrome.Case report: A 60 year old, right-handed man came to our attention due to writer's cramp, bradykinesia and stiffness of his right hand. Neurological examination revealed constant, marked dystonic posturing, rigidity and bradykinesia of the right hand. Hyper-gammaglobulinemia was demonstrated on electrophoresis-serum IgG was increased. Anticardiolipin antibodies were examined by counterimmunoelectrophoresis (ELISA): IgG was negative, while IgM was positive. There was also slight thrombocytopenia. Magnetic resonance imaging brain scan axial T2W/UTSE revealed several hyperintense lesions in the basal ganglia and in the periventricular white matter and diffuse hyperintensity of the subcortical white matter bilaterally in the parietal regions. There was asymmetric parenchimal atrophy, more prominent in the left hemisphere. No clinical improvement was achieved by levodopa, dopamine agonists or anticholinergics. According to the criteria for primary antiphospholipid syndrome our patient had thrombocytopenia and high levels of IgG and IgM anticardiolipin antibodies so he was presumed to have a primary antiphospholipid syndrome.Conclusion: Various movement disorders may appear secondary to stroke, antiphospholipid syndrome, Behcet's disease or brain tumor. These cases may help in the understanding of pathophysiology of movement disorders. Dystonia and parkinsonism as well as other movement disorders may be associated with primary antiphospholipid syndrome.     

Sneddon's syndrome associated with anticardiolipin antibody: a case report.

We report the case of a young man suffering from the rare combination of livedo reticularis and recurrent ischemic cerebrovascular disease (Sneddon's syndrome). He also had a circulating anticardiolipin antibody. in the absence of systemic lupus erythematosus, we suggest the likelihood of a primary antiphospholipid syndrome.     

Retinal migraine,chorea, and retinal artery thrombosis in a patient with primary antiphospholipid antibody syndrome

Summary We report the case of a patient with the unusual combination of migraine, chorea, and retinal arterial thrombosis along with laboratory evidence of autoimmunity. In the absence of systemic lupus erythematosus, the clinical manifestations suggest the presence of the primary antiphospholipid antibody syndrome.     

Lupus anticoagulant and Sneddon's syndrome

We present the coagulation and serological studies of four patients with Sneddon's syndrome, in which antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant) were determined using cardiolipin and a mixture of phospholipid from rabbit brain as antigen for detection of lupus anticoagulant by ELISA. Our results support a relation between Sneddon's syndrome and lupus anticoagulant (IgG subtype) in all cases. The anticardiolipin antibody test was positive only in two cases (one in low level). All patients could be diagnosed as having primary antiphospholipid antibody syndrome. Antiaggregant treatment was not effective in preventing thrombosis in two cases. Three of four patients received long-term oral anticoagulation therapy, with no recurrence of thrombosis observed for a period of at least 3 years.     

Central nervous system Sjögren's syndrome in a child: case report and review of the literature

We describe a case of pediatric Sj?gren's syndrome with progressive neurologic involvement. At age 4 years, she had been diagnosed with Melkersson-Rosenthal syndrome. After being stable with facial diplegia and swelling for 5 years, she acutely presented with diplopia, vertigo, and ataxia. Cranial magnetic resonance imaging (MRI) showed a left dorsal midbrain lesion. Serologic and histopathologic findings confirmed primary Sj?gren's syndrome. She responded well to intravenous methylprednisolone, with subsequent clinical improvement and MRI resolution. This report reviews the pediatric literature and underscores the importance of considering Sj?gren's syndrome in a child with unexplained facial weakness and in the differential diagnosis of pediatric stroke.     

Inflammatory response and the endothelium

Antiphospholipid-mediated endothelium perturbation plays a role in antiphospholipid syndrome (APS)-associated vasculopathy. Antiphospholipid antibodies activate endothelium both in vitro and in vivo experimental models by inducing a pro-inflammatory/-coagulant phenotype; the antibodies recognize β2 glycoprotein I (β2GPI) on human endothelial cells (EC) from different parts of the vasculature.

In spite of such large in vitro evidence, few studies have addressed the issue whether or not a comparable endothelial perturbation might be detectable in vivo.

We investigated several indirect ex vivo parameters of endothelial dysfunction: plasma levels of soluble adhesion molecules (sADM), soluble thrombomodulin (sTM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) by solid-phase assays. The study included: patients with primary antiphospholipid syndrome (n=32), with the syndrome secondary to non-active systemic lupus erythematosus (SLE, n=10), six patients with persistent antiphospholipid positivity at medium/high titre without any clinical manifestation of the syndrome. Fifty-two age and sex matched healthy subjects have been enrolled as controls. In addition, circulating endothelial cells identified by flow cytometry and the brachial artery flow-mediated vasodilation (FMV) were evaluated in 26 patients (20 primary and 6 lupus syndromes) and 30 healthy controls.

Plasma levels of soluble adhesion molecules did not differ from controls, while a significant increase in von Willebrand factor titres (P<0.05) was found. No significant difference was found regarding the number of circulating endothelial cells and flow-mediated vasodilation.

As a whole, these findings do suggest that antiphospholipid antibodies per se are not able to support a full-blown endothelial perturbation in vivo. As shown in antiphospholipid syndrome experimental animal models, a two-hit hypothesis is suggested.     

Clinical and positron emission tomography findings of chorea associated with primary antiphospholipid antibody syndrome.

A fourteen-year-old right-handed male with a history of attention deficit hyperactivity disorder (ADHD) presented with alternating hemichorea. Laboratory findings included elevated anticardiolipin IgG and anti-beta(2)-glycoprotein I IgG, which were consistent with primary antiphospholipid antibody syndrome. Positron emission tomography (PET) imaging revealed altered striatal metabolism in his left putamen while he was exhibiting right-sided hemichorea. His symptoms resolved on prednisone; however, his antiphospholipid antibody profile remained markedly abnormal despite being symptom-free for 26 months.     

A case of SLE presenting the features of antiphospholipid antibody syndrome during a treatment for complicated cryptococcal meningitis]

A 39-year-old woman had developed systemic lupus erythematosus(SLE) at the age of 29. She had a long history of immunosuppressant therapies such as corticosteroid. On admission, she presented a headache due to the cryptococcal meningitis which was confirmed by lumbar puncture. Combined medications of amphotericin B and fluconazole were not effective, and combined amphotericin B and flucytosine were replaced. Prednisolone and methotrexate had been tapered gradually. Fifty days after the initial treatment for meningitis Cryptococcal neoformans was not observed in the cerebrospinal fluid. Sixty days after the treatment, thrombocytopenia was observed with positive lupus anticoagulant and anticardiolipin antibody. Following which, thrombophlebitis occurred in the left brachium. We suggest that the provoked pathoimmunological reaction such as antiphospholipid antibody syndrome during the treatment for meningitis needs to be cared during the course of SLE.     

Systemic lupus erythematosus manifesting as subarachnoid hemorrhage induced by cortical venous thrombosis and followed by medial medullary infarction]

A 43-year-old female, who had been treated for systemic lupus erythematosus (SLE), presented with a subarachnoid hemorrhage (SAH) induced by rupture of cortical venous thrombosis, and be followed by medial medullary infarction during the acute stage of the SAH. The patient initially manifested a SAH. Angiography demonstrated no evidence of any aneurysms or arteriovenous malformations, but revealed cortical venous thrombosis. She suddenly developed left hemiplegia caused by medial medullary infarction on the 6th day. An active anticoagulant therapy was thought to be inappropriate because of initial symptoms as a hemorrhage. Since she had been accompanied by the medullary infarction, then, initially started by antiplatelet therapy. After the confirmation of no saccular or dissecting aneurysms with 2nd angiography, her treatment could be changed to anticoagulant therapy. Because of the sustained negative reactions of anti-cardiolipin beta 2 glycoprotein I antibody and lupus anticoagulant during the course of SLE, the definite diagnosis of antiphospholipid syndrome (APS) could not be made. However, this case is pathogenically thought to be cerebrovascular disease based upon APS, considering that this syndrome may be related to various antigen/antibody systems.     

Antiphospholipid antibodies syndrome in 'Stroke in young'.

Antiphospholipid antibodies syndrome has emerged as an important entity responsible for stroke in young. Seven cases of young stroke (< 40 years of age) with mean age of 30.1 years (age range 25-39 years, 2 males and 5 females), who tested positive for antiphospholipid antibodies are being reported. All subjects had completed strokes. Six had arterial ischaemic and one patient had venous stroke. One patient suffered from four episodes, three ischaemic and one intracerebral haemorrhage. Two patients suffered from foetal loss. Generalised tonic clonic seizures occurred in three patients. Deep vein thrombosis was observed in one case. Thrombocytopenia was not observed in any case. All the patients had elevated anticardiolipin antibodies (aCL) IgM or IgG, while Lupus anticoagulant (LA) was elevated in 4 cases. Six cases belonged to primary antiphospholipid antibodies syndrome and one to lupus like illness. Oral anticoagulants were administered to maintain a high intensity international normalized ratio (INR). No recurrences were observed during a follow up period of 6-18 months.     

Antiphospholipid antibodies and the central nervous system]

Among anti-phospholipid antibodies (APA), anti-cardiolipin antibodies and lupus anticoagulants are associated with arterial and venous thrombo-embolic manifestations. Antiphospholipid antibodies can be secondary to numerous diseases, especially systemic diseases, but they are usually encountered in the primary antiphospholipid syndrome. Neurological manifestations associated with APA are most often, if not always, ischemic in nature: large or small subcortical, often multiple, infarcts and transient ischemic attacks are the usual clinical presentations. Several mechanisms can lead to cerebral ischemia in the primary antiphospholipid syndrome, and their diagnosis is probably important for therapeutic choices. A prospective controlled study has started, which should provide data on the prognosis and management of this syndrome.     

Primary antiphospholipid syndrome presenting with a branch retinal artery occlusion in a 15-year-old boy

Acute vascular events are rare in the pediatric population, but there is an association with the presence of antiphospholipid antibodies. When there is no other underlying medical disorder, this is referred to as primary antiphospholipid syndrome. We present a case of a 15-year-old boy who developed an acute superior branch retinal artery occlusion. Complete evaluation revealed significant elevations in antiphospholipid antibodies. To our knowledge, there are no cases in children of primary antiphospholipid syndrome presenting with this clinical manifestation.     

Different types of antiphospholipid antibodies in AIDS: a comparison with syphilis and the antiphospholipid syndrome.

Alloimmune antiphospholipid antibodies react with phospholipids and are an epiphenomenon of an infectious disease. Most autoimmune antiphospholipid antibodies recognise phospholipid-protein complexes or proteins, such as beta2 glycoprotein I or prothrombin and are related to the clinical features of the antiphospholipid syndrome. Lupus anticoagulant, anticardiolipin antibodies, antiprothrombin, and anti-beta2 glycoprotein I antibodies were studied in 61 human immunodeficiency virus (HIV) patients, 55 syphilis patients, and 45 selected patients with antiphospholipid syndrome. Lupus anticoagulant was present in 72% of HIV and 81% of antiphospholipid syndrome patients. None of the syphilis patients had lupus anticoagulant. Anticardiolipin antibodies were found at comparable prevalence in the three groups (HIV 67%, syphilis 67%, antiphospholipid syndrome 84%). HIV had more frequently anti-beta2 glycoprotein I (13%) and antiprothrombin (12%) antibodies than syphilis (0 and 4%, respectively), but significantly less than antiphospholipid syndrome (61 and 40%, respectively). Autoimmune antiphospholipid antibodies in HIV without clinical features of antiphospholipid syndrome might be a reflex of the immunological chaos and/or the constant antigenic virus stimulus.     

Neurological disease associated with anticardiolipin antibodies in patients without systemic lupus erythematosus: clinical and immunological features

Summary Anticardiolipin antibodies (aCL), one of a group of antiphospholipid antibodies which include the lupus anticoagulant (LA), may occur in association with systemic lupus erythematosus (SLE) and are less commonly detected in other diseases. We retrospectively reviewed the clinical and immunological features of 39 consecutive patients with abnormal aCL identified by one laboratory, to examine the spectrum of neurological disease in those patients without SLE. Fourteen patients in this category are described, 6 of whom did not have evidence of LA. All but 1 presented with neurological symptoms. Stroke and migraine dominated the clinical presentation, but many patients had features to suggest the presence of a hypercoagulable state. This study lends support to the concept of a primary antiphospholipid syndrome.