Myopathy secondary to intravascular large B-cell lymphoma

We report a case of a 78-year-old woman presenting with progressive proximal muscle weakness mainly to lower limbs and myopathic EMG associated with intravascular large B-cell lymphoma.Muscle biopsy showed myopathic changes, intravascular large B-cell lymphoma but no inflammation or fibre necrosis; the patient’s serum cross-reacted with an unidentified nuclear antigen of approximately 45 kDa present in muscle and lymphoma cells.Our case illustrates a myopathy associated with intravascular large B-cell lymphoma probably mediated by antibodies cross-reacting with a nuclear protein expressed by neoplastic cells and normal muscle. The nature of this nuclear antigen remains unidentified.     

Recombinant human erythropoietin shortens the uraemic bleeding time without causing intravascular haemostatic activation

Blood rheology and haemostasis have been investigated in 8 haemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). The aim was to elucidate the mechanism by which rHuEPO improves haemostasis, and to determine whether rHuEPO promotes intravascular coagulation. Investigations were performed before, and after 3 months of treatment. Haemoglobin and haematocrit rose significantly after rHuEPO (p less than 0.001) and there was a concurrent shortening of the bleeding time. No significant changes were observed in platelet aggregation, thromboxane generation, or platelet nucleotide content during the treatment period. Whole blood viscosity increased following rHuEPO (p less than 0.01), but plasma viscosity and red cell deformability were unchanged, as were markers of intravascular platelet activation and plasma levels of cross-linked fibrin derivatives. No patient suffered from thrombosis during the study period, and elevation of the haematocrit in uraemic patients up to 0.35 with rHuEPO did not appear to lead to intravascular coagulation. Shortening of the prolonged bleeding time in haemodialyzed patients following rHuEPO appeared to be due to the increase in circulating red cells, rather than to changes in platelet reactivity.     

Angiotropic intravascular large-cell lymphoma with massive cerebral extension.

Angiotropic intravascular large-cell lymphoma (AILL) is a rare, generally fatal disease characterised by a multifocal proliferation of neoplastic mononuclear cells within small blood vessels. The diagnosis of a patient was made at necropsy. The malignant cells had infiltrated the periventricular areas of the brain.     

A patient with intravascular malignant lymphomatosis presenting subacute dementia one year after sustained urinary retention and high serum LDH activity from the onset]

We report a 71-year-old man with intravascular malignant lymphomatosis who showed high serum LDH and urinary disturbance for one year before manifesting dementia. High serum LDH was found at a health check at age 70. Two months later, he had an onset of backache and urinary retention. MRI of the spinal cord was unremarkable. One year later, he showed decline of mental activities and was admitted to our hospital. He was agitated and confused. However cranial nerve palsy or limb weakness was not noted. The MRI of the brain showed T2-high signal in bilateral occipital, right temporal lobe and the left insular cortices. The abdominal CT scan showed swelling of the adrenals on both sides. Adrenal biopsy revealed diffuse large B cell lymphoma. He developed respiratory distress and he died two months after the admission. Post mortem examination revealed intravascular and extravascular proliferation of lymphoma cells in most of the internal organs including adrenals, spleen, liver and the kidneys. In the brain, the laminar necrosis was seen in the left occipital cortex and hemorrhagic infarctions were noted in the insular and temporal cortices and the medial temporal cortex. Sacral spinal cord showed necrosis of the gray matters and loss of myelinated fibers in the white matter. Intravascular proliferation of the lymphoma cells were also seen in the vessels of the brain and the spinal cord. This patient suggests the importance of survey for intravascular malignant lymphomatosis, when high serum LDH and myelopathy of lumbosacral area are seen.     

Intravascular lymphoma mimicking vasculitis

Intravascular lymphoma is a rare malignancy which is characterized by a proliferation of atypical appearing B cells, generally confined to vascular lumina. A tissue biopsy demonstrating the pathology is required to make a diagnosis. The tumor is often disseminated at the time of diagnosis and prognosis is poor, even with aggressive chemotherapy. Neurologic presentations of this neoplasm can be quite varied. This report documents the presence of intravascular lymphoma diagnosed on a brain biopsy in a 60-year-old man. He initially presented 6 months before brain biopsy with chest pain and hypotension, warranting coronary artery bypass graft surgery. Four months later, he presented with signs attributed to a stroke (diaphoresis, slumped over in a chair and left hand weakness). He subsequently developed a sudden onset wide-based gait, left leg numbness, word finding difficulties and worsening confusion. A MRI study showed multiple infarcts in the brain, including cerebellum. Invasive angiogram suggested vasculitis. He was started on a course of treatment for presumed central nervous system vasculitis. He continued to develop signs suggestive of ongoing infarct development and a biopsy from the right parietal was taken. The biopsy showed atypical intravascular CD20 positive staining B cells, consistent with intravascular lymphoma.     

Studies of the endothelial origin of cells in systemic angioendotheliomatosis and other vascular lesions of the brain and meninges using ulex europaeus lectin stains

Ulex europaeus agglutinin I (UEA-I) is a plant lectin which binds specifically to alpha-L-fucose moieties on the surface glycoproteins of human endothelial cells. The binding is completely inhibited by preincubation of the lectin with fucose. UEA-I can be conjugated directly to fluorescein or peroxidase and can be used to stain endothelium of paraffin embedded tissues. UEA-I staining was evaluated on normal and infarcted brain, systemic angioendotheliomatosis, metastatic epidural angiosarcoma, hemangioendothelioma, hemangioblastoma, angioblastic meningioma of both the hemangioblastic and hemangiopericytic types, and vascular meningioma. The endothelium, but not neuropil of normal and infarcted brain was positive for UEA-I. The tumor cells of hemangioendothelioma and angiosarcoma also stained. However, no staining was seen in malignant intravascular cells of angioendotheliomatosis, the stromal cells of hemangioblastoma, or pericytes of angioblastic meningioma. It is concluded that the malignant cells in angioendotheliomatosis, the stromal cells of hemangioblastoma and the pericytes of angioblastic meningioma do not produce surface glycoproteins characteristic of endothelial cells.     

Effect of platelet antiserum on the activation of intravascular coagulation by endotoxin.

The importance of platelets in the activation of endotoxin-induced intravascular coagulation was investigated in rabbits made severely thrombocytopenic by an intravenous injection of platelet antiserum. Goat antiserum removed more than 98% of the circulating platelets. If two doses of endotoxin were injected intravenously into thrombocytopenic rabbits, renal glomerular microclots still occurred, but coagulation analysis showed a definite reduction of intravascular coagulation. The occurrence of microclots after endotoxin injection into thrombocytopenic rabbits could be prevented by continuous infusion of heparin. The treatment of another group of rabbits with the threefold dose of antiserum prevented the occurrence of renal glomerular microclots after endotoxin injection. No correlation between platelet counts prior to the second dose of endotoxin and the occurrence of glomerular microclots could be demonstrated. With this study, the importance of platelets in triggering endotoxin-induced generalized intravascular coagulation becomes doubtful. The effect of platelet antiserum in preventing the occurrence of generalized intravascular coagulation may depend on its influence on other mechanisms important in activating intravascular coagulation by endotoxin.     

脑血管支架置入者血小板活化和炎性因子与血管再狭窄的关联

目的：探讨脑血管支架置入后血小板活化和炎性因子的变化与再狭窄的关系。 方法：以颅内动脉,支架,狭窄,血小板活化,炎症因子为检索词,检索中国期刊全文数据库(1999-01/2009-06);以intracranial arterial, stents, stenosis, elevated platelet activation, inflammatory factors为检索词,检索PubMed数据库(1999-01/2009-06),文献检索语种限制为中文和英文。以血小板的活化和炎症因子的变化为评价指标。纳入脑血管支架置入治疗颅内动脉狭窄的临床研究,排除动物实验和其他治疗颅内动脉狭窄的方法。 结果：计算机初检得到650篇文献,根据纳入排除标准,对脑血管支架置入后血小板活化和炎性因子的变化与再狭窄的关系进行分析。血小板活化、炎性反应和炎症因子在颅内外血管狭窄支架置入后再狭窄中的作用,目前成为研究的热点。认识支架置入后再狭窄的危险因素对判断支架置入的适应证及有效预防支架置入后再狭窄有重要意义。血小板血栓形成是支架置入后急性血管闭塞的主要原因之一,活化的血小板通过其释放产物加重对内皮细胞的破坏作用,促进平滑肌细胞的过度增殖、迁移。支架本身作为一种外来刺激物,首先引起血小板在支架表面的聚集和激活,分泌出大量的各种细胞因子,导致血栓的形成。随之大量的白细胞将在血管损伤部位聚集后分泌出细胞因子并介导炎症反应,导致平滑肌细胞大量向损伤部位迁移发生增殖反应,由于新生内膜的大量增生,导致血管壁的重构引起支架内再狭窄。 结论：置入前常规给予抗血小板治疗,同时控制置入后炎症反应、抑制血管平滑肌细胞增殖将会成为治疗颅内血管狭窄支架置入后再狭窄的有效方法。     

Analysis of the disappearance curve of labelled fibrinogen at the time of hyperfibrinogenemia in rabbits with acute or chronic intravascular coagulation.

In order to study fibrinogen metabolism, the disappearance curve of 125I-abelled homologous fibrinogen was investigated in the rabbits with experimentally induced acute or chronic intravascular coagulation by injection of Lycopodium spores or thromboplastin. The results obtained were as follows. 1. Using haemolysate, an intermediate phase with upward convexity was clearly recognized between the early rapid-decay phase and the late slow phase in each radioactivity decay curve obtained in groups of rabbits. This convexity was most marked with acute intravascular coagulation induced by injection of Lycopodium spores, and was less marked, although higher, with chronic intravascular coagulation induced by injection of thromboplastin than that in the normal control. 2. The disappearance curve with the intermediate phase could be expressed, in approximation, as a sum of 2 equations--the initial exponential decay equation and the late parabolic one. 3. From the results obtained by separate examinations of the disappearance curve of plasma, fibrin clots and serum in rabbits with acute intravascular coagulation induced by injection of Lycopodium spores, the intermediate phase appears to be influenced more by the secondary increase of labelled non-clottable part tahn recirculation of the labelled fibrinogen. 4. The half time (27.4 hours) of the radioactivity in fibrin clots at the late phase observed in the group of rabbits with acute intravascular coagulation induced by injection of Lycopodium spores was shorter than that in the normal rabbits (50.2 hours). This fact may indicate that the increase of fibrinogen in the group of rabbits with acute intravascular coagulation induced by the injection of Lycopodium spores is due to overproduction of fibrinogen. 5. The half time of labelled fibrinogen should be calculated from disappearance curve of fibrin clots, instead from that of haemolysate or plasma.     

Cellular sources of tissue factor in endotoxemia and sepsis

Sepsis is a systemic host response to infection by pathogenic microorganisms. Activation of the coagulation cascade during endotoxemia and sepsis leads to disseminated intravascular coagulation. This review focuses on tissue factor expression by hematopoietic and non-hematopoietic cells and its contribution to the activation of coagulation during endotoxemia and sepsis.     

Sonographic diagnosis and endovascular recanalization of the internal carotid artery in a patient with carotid thromboembolism following coiling of cerebral aneurysm

Thromboembolism after brain aneurysm embolization involves high morbidity/mortality and its conservative treatment is still a standard policy. We report the practical utility of transcranial colour-coded Doppler sonography (TCCS) in the early diagnosis and effectiveness of prompt intravascular intervention in the treatment of this condition. A 50-year-old woman developed acute neurological deficit after intravascular re-embolization of a brain aneurysm. Severely decreased blood flow velocity in the middle cerebral artery was revealed with TCCS and angiography confirmed nearly complete occlusion of the carotid artery. After heparin administration, intravascular thrombectomy was performed at the same session with implantation of a stent. The symptoms faded away within hours and the patient recovered fully. Prompt intravascular intervention could be a valuable and efficient alternative in the treatment of thromboembolism after embolization of cerebral aneurysm. TCCS enables early differential diagnosis of this potentially devastating sequel.     

Intravascular malignant histiocytosis mimicking central nervous system vasculitis: An immunopathological diagnostic approach

A 53-year-old man presented with a lumbosacral polyradiculoneuropathy and developed fluctuating encephalopathy suggestive of multifocal small vessel disease. Postmortem examination demonstrated multifocal vascular occlusions by undifferentiated cells confined to the intravascular space. Extravascular spread was found only in spleen and liver. The presence of lysozyme and absence of factor VIII in the cytoplasm of the malignant cells confirmed their histiocytic nature. This patient had an unusual intravascular form of malignant histiocytosis that must be included in the differential diagnosis of multifocal vascular disease.     

Neuropathology of malignant lymphoma and its related disorders]

Primary central nervous system lymphoma are characterized by macroscopically the tumor mass formation in the cerebral hemisphere including basal ganglia and corpus callosum and diffuse invasion particularly in the periventricular region, and microscopically lymphoma cells proliferation around the vessels and diffuse invasion into the brain parenchyma. Secondary involvement of central nervous system by systemic lymphoma are characterized by tumor cells invasion to the meninges and cranial and spinal nerve roots and tumor cells invade to the brain parenchyma along the perivascular space. Tumor nodule formation are very rare and tumor cells are not found in the lumen of the vessels. In the cases of extradural metastasis of systemic lymphoma, in addition to spinal cord compression, secondary circulatory disturbance, particularly venous congestion are also important factor for the spinal cord damages. In intravascular malignant lymphoma, not only tumor cells proliferation in the lumen of small sized vessels, but also secondary vasculitis and fresh and old thrombus formation are important for the development of multiple infarction of central nervous system. And spinal cords particularly in the levels of lumbosacral spinal cord are dominantly involved. Recently, according to the longness of clinical course of intravascular malignant lymphomatosis, cases with tumor mass are reported and these tumor mass are very similar to that of primary central nervous system lymphoma.     

5000/3－羟基丁酸与3－羟基己酸共聚酯在心血管组织工程中应用的试验研究（英文自译）

背景：可降解聚合材料3-羟基丁酸与3-羟基己酸共聚酯(3-hydroxybutyrate-co- 3-hydroxyhexanoate, PHBHHx)具有良好的机械性能和生物可降解性。 目的：在体研究PHBHHx的血管内生物相容性。 方法：采用脱细胞羊肺动脉为支架,以PHBHHx涂层,构建复合补片,植入新西兰兔腹主动脉内,以脱细胞未涂层羊肺动脉片作为对照。分别于植入后第1,4,12周取出移植补片进行组织学、免疫荧光染色、扫描电镜和钙含量测定。 结果与结论：复合补片管腔面光滑无血栓,内膜增生适度,再细胞化完全;免疫荧光染色可见新生内膜组织中类内皮细胞呈CD31阳性反应,单层连续排列,间质细胞呈平滑肌肌动蛋白阳性反应;复合补片的钙含量明显低于未涂层羊肺动脉片。说明PHBHHx的血管内生物相容性满意,是心血管组织工程较为理想的腔内涂层材料。     

Directed glia‐assisted angiogenesis in a mature neurosensory structure: Pericytes mediate an adaptive response in human dental pulp that maintains blood‐barrier function

The specialized tightly controlled microcirculation of craniofacial neurosensory organs is an essential evolutionary adaptation and yet a dilemma where angiogenic remodeling occurs. Despite extreme plasticity of neurosensory structures, the capacity to reconcile barrier phenotype of the microcirculation with an angiogenic cascade is not known. Here we provide primary evidence for such a response in an elemental neurosensory structure, human dental pulp, following chronic carious insult. In response to hypoxic challenge neurosensory odontoblasts express hypoxia‐inducible factor‐1α and notch‐1. Associated radial rearrangement of astrocyte‐like telacytes that communicate through a cell‐poor zone with the microvasculature is observed. Activated pericytes characterized by expression of α‐smooth muscle actin are located adjacent to the telacyte attachment to the vasculature. In this location, endothelial expression of sonic hedgehog parallels expression of notch‐1 by pericytes. The angiogenic response is initiated by pericyte contraction and altered endothelial polarity and proliferation leading to intussusception of endothelial cells and extensive remodeling of basement membrane with upregulation of laminin‐8 and laminin‐5. These responses guide intravascular loop formation that maintains both intact basement membrane and tight junctions. This initial phase is followed by formation of anastomoses that enhance the hemodynamic capacity of the intravascular loops. The formation of anastomoses is mediated by extension of cytonemes from pericytes guided by MHC‐II⁺/CD‐163⁺ microglia aligned with the telacytes. The cytonemes seek out pericytes on adjacent intravascular loops to initiate migration of endothelial cells. These findings support a new paradigm for understanding angiogenic capacity of neurosensory structures and aberrations of this response manifest as neurovasculopathies. J. Comp. Neurol. 520:3803–3826, 2012. © 2012 Wiley Periodicals, Inc.     

Intravascular lymphomatosis of the brain: a diagnostic problem.

Intravascular lymphomatosis (of B- or T-cell origin) is a rare lymphoproliferative disorder characterised by neoplastic proliferation of lymphoid cells within the lumen of capillaries, small veins and arteries with no or minimal involvement of the parenchyma. Its predilection sites are the skin and the brain. We studied a 44-year-old man who presented with a 2 year history of unexplained LDH elevation followed by a neurological syndrome without systemic involvement. Brain biopsy showed an intravascular lymphoma of the B-cell lineage. This report illustrates the diagnostic challenge of this rare disorder with a grim prognosis.     

An autopsy case of lymphomatosis cerebri showing pathological changes of intravascular large B‐cell lymphoma in visceral organs

We describe the case of a 61‐year‐old man presenting with subacute encephalopathy. The clinical manifestations included progressive dementia and pyramidal and extrapyramidal tract signs. Brain CT scan and MRI showed diffuse bilateral white matter changes in the cerebral hemispheres, basal ganglia, thalamus and brainstem. No contrast‐enhanced lesion was observed. Peripheral blood studies, CSF analysis, and brain and muscle biopsies were nonspecific and failed to reveal diagnostic evidence of any specific disease. The patient was diagnosed with and treated for a cerebral demyelinating disorder. Post mortem examination showed diffuse infiltration of lymphoma cells without mass lesions in the extensive cerebral white and gray matter with minimal intravascular patterns, particularly in the perivascular and periventricular spaces. These findings were consistent with lymphomatosis cerebri (LC). In other visceral organs such as the lungs, liver, kidneys and adrenal glands, blood vessels were plugged by numerous neoplastic cells which were morphologically and immunohistochemically similar to those observed in the CNS, consistent with intravascular malignant lymphoma (IVL). To our knowledge, this is the first autopsy report showing the coexistence of LC and IVL. This case suggests a possible link between LC and IVL.     

Intravascular lymphomatosis presenting with sudden hearing loss

Intravascular lymphoma (IVL) is a rare disorder characterized by the aggregation of malignant large cell lymphoma cells in small vessels. Neurological manifestations are typically the initial and, often the only, clinically obvious consequences of this malignancy. Diagnosis is dependent on biopsy or postmortem demonstration of the intravascular tumor. We report a patient in whom sudden hearing loss heralded IVL and propose that the hearing loss may have been the consequence of labyrinthine infarction consequent to the aggregation of malignant cells in the internal auditory artery.     

Enhanced effect of inhibition of thrombin on endothelium in murine endotoxaemia: Specific inhibition of thrombocytopenia

Introduction

In systemic endotoxaemia, bacterial lipopolysaccharide causes the rapid expression of tissue factor (TF) and disseminated intravascular coagulation and in animal models, anticoagulants limit pathology and promote survival. Recent studies have emphasised the importance of TF expressed by mononuclear cells for initiating thrombin generation during endotoxaemia and suggested that endothelial cell TF is of little relevance. However, the precise importance of endothelium for intravascular thrombin generation has not been established. In this study, we compared the effect of equivalent levels of hirudin tethered to either endothelium or platelets and monocytes.

Materials and Methods

CD31-Hir-Tg mice express a vesicle-targeted, membrane-tethered hirudin fusion protein on endothelium, platelets and monocytes. Bone marrow chimeras between these mice and C57BL/6 were generated The level of intravascular hirudin expressed during endotoxaemia was quantified by inhibition studies using an anti-hirudin antibody and reference to the circulating thrombin anti-thrombin complexes generated in control mice given soluble hirudin.

Results and Conclusions

Antibody inhibition studies indicated that individual chimeras expressed similar levels of hirudin fusion protein on endothelium alone as on platelets and leukocytes combined and accordingly, the levels of thrombin anti-thrombin complexes and fibrinogen in each chimera were similar, indicating equivalent inhibition of thrombin generation. However, mice with hirudin on endothelium alone developed significantly less thrombocytopenia. These results suggest a hitherto unrecognized role of endothelium in thrombin-dependent platelet sequestration during endotoxaemia. The data have implications for the development of therapeutic strategies based on targeted anticoagulation to limit disseminated intravascular coagulation.