Catastrophic antiphospholipid syndrome masquerading as ischaemic colitis

We describe a young woman whose initial presentation was dominated by acute diarrhoea. Life-threatening multiorgan failure rapidly ensued and necessitated mechanical ventilation and dialysis treatment. An initially elongated activated partial thromboplastin time prompted further coagulation tests that led to the detection of positive lupus anticoagulant, a highly elevated IgG-anticardiolipin (aCL) antibody titre, and prolonged dilute Russell's viper venom time. Histological examination of samples obtained during endoscopy revealed widespread intestinal thrombotic microangiopathy. In view of these serologic and histologic features, a diagnosis of the malignant variant of the antiphospholipid syndrome (APS), also termed 'catastrophic APS', was established. In spite of this syndrome's grim prognosis, the patient recovered following intensive anticoagulation and adjunct treatment with steroids and immunoglobulins.     

A unique case of sporadic Creutzfeldt-Jacob disease presenting as progressive supranuclear palsy

We report a Japanese case of sporadic Creutzfeldt-Jakob disease (CJD) presenting as progressive supranuclear palsy. For 2 years after onset, neurological deficits had slowly progressed but neither myoclonus nor periodic synchronous discharge was observed. Diffusion-weighted image (DWI) showed unique high signal lesions in the bilateral frontal cortex, left parietooccipital and occipital cortices, but there was nearly no change eight months later. Needle biopsy revealed deposition of prion protein of a patchy/perivacuolar type with spongiform degeneration. Thus, the phenotype of sporadic CJD seems variable and DWI should be performed, even in atypical cases lacking the characteristics of CJD.     

进行性核上性麻痹的临床表现和神经影像学特点

目的探讨进行性核上性麻痹(progressive supranuclear palsy,PSP)的临床特点及头颅MRI、正电子发射体层扫描(PET)检查在本病中的诊断价值。方法回顾性分析19例PSP患者临床特点、神经影像学特征。结果19例PSP患者中,12例患者以走路不稳、反复向后跌倒为首发.17例患音出现垂直性核上性眼肌麻痹,假性球麻痹出现较早,还伴有轴性肌张力障碍、轻度痴呆等症状。19例患者均行头颅MRI检查,10例患者正中矢状位可见中脑上端萎缩,呈"蜂鸟征",水平位可见中脑前后径变小,呈"鼠耳征",1例患者中脑被盖和顶盖部T_2加权像显示弥散性高信号,中脑萎缩随病程加重。13例患者PET检查,均可见中脑葡萄糖代谢降低,双侧额叶葡萄糖代谢降低比较明显,部分合并顶叶或顶枕联合区葡萄糖代谢降低。结论 PSP临床表现变异较大,但通过头颅MRI、PET等辅助检查的特征性表现,可为诊断及鉴别诊断提供依据。     

IVIG treatment for progressive stroke in the primary antiphospholipid antibody syndrome

A 32-year old woman with antiphospholipid antibody syndrome (APS) developed severe thrombocytopenia, elevated liver enzymes and progressive cerebral thrombosis a few days after preterm delivery by caesarean section. Her condition deteriorated despite treatment with low dose aspirin, anticoagulation by heparin and iv glucocorticoid administration. Intravenous immunoglobulin (IVIG) on three consecutive days was followed by rapid resolution of her neurological impairment and increasing platelets counts. The temporal association between IVIG and reversal of both neurological impairment and platelet number strongly indicates a specific effect of IVIG administration in this condition. It is proposed that IVIG therapy is considered as a therapeutic option in APS patients with progressive cerebral infarction despite optimal use of anticoagulant and immunomodulating agents.     

Primary antiphospholipid syndrome

An antiphospholipid antibody (APLA) syndrome has been proposed for those patients with systemic lupus erythematosus (SLE) or with other connective tissue diseases who have APLA and manifestations that seem related to their effect (venous thrombosis, arterial occlusions, thrombocytopenia, hemolytic anemia, recurrent fetal loss, leg ulcers, and livedo reticularis). Occurrence of a primary antiphospholipid syndrome has also been mentioned but not defined. We present 9 young patients who had at least 2 of the clinical manifestations that have been related to high titers of APLA, but had neither SLE nor other recognizable connective tissue disease. We propose criteria for diagnosis of such a primary antiphospholipid syndrome and discuss the possible mechanisms whereby a single autoantibody can cause systemic disease.     

Amantadine-induced myoclonus in a patient with progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a tauopathy that generally results in a hypokinetic disorder. Treatment is largely symptomatic, with some small studies indicating a benefit with dopaminergic therapy. Myoclonus is a hyperkinetic disorder that can be seen as part of later stage Parkinson's disease and in multiple system atrophy, but is rarely seen in PSP. Here we report a case of myoclonus precipitated by amantadine in a patient with PSP.     

Neuropsychological comparison between corticobasal degeneration and progressive supranuclear palsy

We conducted a neuropsychological comparison among cases with corticobasal degeneration (CBD; n = 8), those with progressive supranuclear palsy (PSP; n = 5) and healthy control subjects (n = 12) using an extensive neuropsychological battery assessing memory and executive functions. There were no significant differences among three groups for age, education, scores on the Mini-Mental State Examination and Zung's self-rating depression scale. Both patient groups showed retrieval impairment without recognition difficulties, and a dysexecutive syndrome. Along with those similarities, we observed some differences between CBD and PSP patients. Memory impairments in CBD patients were more marked than PSP patients in Rey's complex figure test, while they were less prominent in Rey's auditory verbal learning test. Perseverative errors of Nelson in Wisconsin card sorting test (Keio version) were more marked in CBD patients than in PSP patients. These two diseases showed memory and executive dysfunctions probably due to subcortico-frontal dysfunction. Some neuropsychological differences may help to distinguish CBD clinically from PSP.     

Striatal phosphoproteins in Parkinson disease and progressive supranuclear palsy.

This study was undertaken to evaluate the levels of cAMP-regulated phosphoproteins in the striatum of patients with neurodegenerative diseases of the dopaminergic system. Postmortem samples of caudate nucleus and putamen from 24 control subjects, 23 patients with Parkinson disease, and 13 patients with progressive supranuclear palsy were studied with immunoblotting techniques. The levels of tyrosine hydroxylase were reduced in patients with Parkinson disease (levels were 24% and 10% of controls in caudate nucleus and putamen, respectively) and with progressive supranuclear palsy (levels were 11% and 6% of controls in caudate nucleus and putamen, respectively). Five phosphoproteins, which are present in striatal neurons and are likely to play a role in the postsynaptic actions of dopamine, were measured. These included ARPP-16, ARPP-19, ARPP-21 (cAMP-regulated phosphoproteins of Mr 16,000, 19,000, and 21,000, respectively), DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32,000), and phosphatase inhibitor I. The levels of these phosphoproteins were inversely correlated with postmortem delay. In brains of patients with Parkinson disease or progressive supranuclear palsy with postmortem delays comparable to those of controls, the levels of these proteins as well as those of synaptic (synapsin I and synaptophysin) and glial (glial fibrillary acidic protein and myelin basic protein) markers were not significantly modified. We conclude that the levels of several phosphoproteins involved in signal transduction in striatal neurons are not altered in Parkinson disease and progressive supranuclear palsy. This observation supports the view that the striatal output neurons are intact in both diseases.     

Antiphospholipid antibody and antiphospholipid antibody syndrome.

Over the past year, many reports have been published on a variety of clinical manifestations related to antiphospholipid antibodies. The low prevalence of anticardiolipin antibodies with the rare occurrence of thrombosis and a low rate of fetal loss in studies in Malaysia and China showed a potential role for local factors. A study of cross-reactive idiotype of the anticardiolipin antibody suggested that anticardiolipin antibodies are derived from a set of natural autoreactive clones. Regarding the pathogenic role of the antiphospholipid antibody, evidence has been presented that the epitopes formed between cardiolipin and beta 2 glycoprotein I are the targets of the antiphospholipid antibody. Complement activation, abnormalities of natural anticoagulants such as protein S deficiency, and genetic association with DR4, DR7, and DRw53 have also been studied.     

Primary prevention in antiphospholipid antibody carriers

The discovery of antiphospholipid antibodies (aPL) positivity in individuals who have never experienced thrombosis or pregnancy complications is not a rare event, and is one of the unresolved issues in the field of antiphospholipid syndrome (APS). This paper focuses on primary prophylaxis for thrombotic events in aPL carriers. In our view, patients with high risk aPL profiles and/or other cardiovascular risk factors, concomitant diagnosis of systemic lupus erythematosus (SLE) and patients with an history of obstetric APS (OAPS) should be offered thromboprophylaxis. Chronic thromboprophylaxis with low-dose aspirin and hydroxychloroquine in aPL positive SLE patients should be prescribed both to prevent thrombosis and to avoid early organ damage.     

进行性核上性麻痹的脑葡萄糖代谢研究

 目的 探讨进行性核上性麻痹（PSP）患者¹⁸F-脱氧葡萄糖正电子发射体层 (¹⁸F-FDG PET)脑显像特点及与临床特征的相关性。方法 对13例PSP患者和30例相匹配的健康对照者进行脑¹⁸F-FDG PET检查,应用视觉分析法与统计参数图（SPM）分析法比较2组脑葡萄糖代谢的差异。结果 与对照组相比,PSP患者脑¹⁸F-FDG PET显像视觉分析法显示双侧额叶皮质、中脑、皮质下核团如基底节、丘脑示踪剂摄取减少,SPM分析显示双侧双侧额上、中回、额叶内侧部皮质、扣带回、中脑及皮质下结构,基底节、丘脑葡萄糖代谢减低,与患者眼球垂直运动障碍、姿势障碍、肌张力增高及认知功能障碍等临床症状相一致。结论 结合临床症状,应用¹⁸F-FDG PET脑显像有助于PSP的早期诊断。     

Proton magnetic resonance spectroscopy in corticobasal degeneration and progressive supranuclear palsy

Background:   Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) each have distinctive clinical features, but diagnosis is often uncertain. Our purpose was to evaluate whether localized, single-voxel proton magnetic resonance spectroscopy (¹H-MRS) could distinguish between typical CBD and PSP patients.
Methods:   The study included 10 patients with CBD, nine with PSP and eight age-matched normal healthy subjects. A single-voxel method of 8 cm³ (2 × 2 × 2 cm) was used for ¹H-MRS. The volume of interest was selected at the frontoparietal cortex and the lentiform nucleus.
Results:   Patients with CBD had significantly reduced ratios of N-acetylaspartate to choline-containing compounds (NAA/Cho), N-acetylaspartate to creatine and phosphocreatine (NAA/Cr) in the frontoparietal cortex and lentiform nucleus compared with the normal subjects. Patients with PSP had significantly reduced NAA/Cho and NAA/Cr ratios in the lentiform nucleus, but not in the frontoparietal cortex compared with normal subjects. There was a significant difference in the NAA/Cho in the frontoparietal lobe between CBD and PSP patients.
Conclusion:   ¹H-MRS may indicate different regional patterns of neuronal involvement in CBD and PSP. We suggest that this could be helpful in the differentiation and diagnostic evaluation of CBD and PSP patients.     

Pathogenetic mechanisms of antiphospholipid antibody production in antiphospholipid syndrome

Antiphospholiipid syndrome (APS) is an autoimmune disease characterized by the pathological action of antiphospholipid antibodies (aPL), that leads to recurrent pregnancy loss and thrombosis. Despite limited evidence, it is clear that there are both inherited and acquired components of the ontogeny of these antibodies. Animal genetic studies and human familial and population studies highlight the influence of genetic factors in APS, particularly human leukocyte antigen associations. Similarly, both animal and human studies have reported the importance of acquired factors in APS development and infectious agents in particular have a great impact on aPL production. Bacterial and viral agents have been implicated in the induction of autoimmune responses by various mechanisms including molecular mimicry, cryptic autoantigens exposure and apoptosis. In this review we highlight the latest updates with regards to inherited and acquired factors leading to the manufacturing of pathogenic antibodies and APS.