Atypical Young-onset Dementia in Cerebral Thromboangiitis Obliterans: A Case Report.

Young-onset dementia (YOD, age at onset below 45 y) has a broad differential diagnosis. We describe a 41-year-old man with atypical manifestations of YOD syndrome in cerebral thromoboangiitis obliterans (CTAO). Extensive antemortem workup including clinical assessment, laboratory investigations, neuroimaging, and genetic testing did not elucidate a diagnosis. Postmortem neuropathologic examination revealed cortical sickle-shaped granular atrophy, resulting from numerous remote infarcts and cortical microinfarcts that mainly affected the bilateral frontal and parietal lobe, confirming CTAO. Although CTAO is a rare cause of vascular dementia, it should be considered as one of the differentials in patients with YOD with a history of heavy smoking and presence of symmetric damages of watershed-territory on neuroimaging.

Thromboangiitis Obliterans (Buerger's Disease) in an Adolescent Male.

Arterial occlusive disease of the limb is very rare in children. Buerger's disease (BD) is a nonatherosclerotic, segmental inflammatory arteritis affecting the small and medium-sized vessels of the extremities. We report BD in a 16-year-old male presenting with arterial insufficiency of left foot and history of smoking cigarettes and cannabis for 2 years. BD was diagnosed based on history of smoking in combination with clinical, laboratory, and radiologic findings. Pediatric hemato-oncologists should consider BD in the differential diagnosis in adolescents who smoke cigarettes and/or cannabis and present with vascular insufficiency of the hands and/or feet.

[THROMBOANGIITIS OBLITERANS OVERLAPPING WITH ATHEROSCLEROTIC OCCLUSIVE ARTERIAL DISEASE: SMALL MESENTERIC ARTERY INVOLVEMENT BY THROMBOANGIITIS OBLITERANS].

INTRODUCTION: Thromboangiitis obliterans is an inflammatory occlusive vascular disease of young smokers that commonly involves the small and medium sized arteries and veins of the extremities. An important differential diagnosis of thromboangiitis obliterans is atherosclerotic arterial disease. An atypical presentation of thromboangiitis obliterans by involvement of mesenteric arteries has been described sporadically. CASE PRESENTATION: We report the case of a patient presenting with Raynaud's phenomenon, ischemia of the upper and lower extremities, as well as mesenteric ischemia. The dramatic course of the disease advanced to gangrene of the calves and intestinal infarction. In this patient, angiographic and histologic features were consistent with thromboangiitis obliterans associated with atherosclerotic arteriopathy. DISCUSSION: A review of the literature revealed 31 reported cases of mesenteric artery involvement by thromboangiitis obliterans. The overlap between thromboangiitis obliterans and atherosclerotic arteriopathy is rare but has recently focused attention in the literature. CONCLUSION: In the differential diagnosis of mesenteric ischemia, thromboangiitis obliterans is a rare but important diagnosis that should be considered. In view of shared features of thromboangiitis obliterans and peripheral artery disease, awareness of their possible coexistence is needed in order to make the right diagnosis and offer proper treatment.

[Cerebral manifestations of thromboangiitis obliterans. Case report]. / Thromboangitis obliterans agyi manifesztációja.

Thromboangiits obliterans (Buerger's disease) is a non-atherosclerotic, segmental inflammatory and obliterative disease affecting small and medium sized arteries and veins. The etiology is still unknown, but it is in close relationship with tobacco use. Symptoms begin under the age of 45 years and the undulating course is typical. Patients usually present with acute and chronic ischemic or infectious acral lesions. Diagnosis is usually based on clinical and angiographic criteria and it is important to exclude autoimmune disease, thrombophilia, diabetes, and proximal embolic sources. Even though Buerger's disease most commonly involves the arteries of the extremities, the pathologic findings sometimes affect the cerebral, coronary and internal thoracic, renal and mesenteric arteries as well. The authors present the history of a patient with known Buerger's disease and acute ischemic stroke. Brain imaging detected acute and chronic ischemic lesions caused by middle cerebral non-atherosclerotic arteriopathy on the symptomatic side. Other etiology was excluded by detailed investigations. Orv. Hetil., 2016, 157(30), 1207-1211.

Hypoxia-inducible factor-1α expression in the different stages of rat thromboangiitis obliterans.

We investigated the expression and effects of hypoxia-inducible factor-1α (HIF-1α) in rat thromboangiitis obliterans (TO). Rats were divided into sham and model groups. The model group was further divided into groups based on observation duration. Lauric acid was injected below an artery clamp to simulate TO in the model group; saline was used in the sham group. Clamps were removed 15 min after injection in both groups, and physiological changes were observed at different times (gross observation and hematoxylin and eosin staining). The animals were killed at various times following the operation and serum and muscle tissues were sampled. For the sham group: the endometrium was relatively intact; medial membrane and epineurium lesions were absent; and blood vessels and surrounding tissues had no inflammatory cell infiltration. For the model group: all subgroups displayed inflammation; large numbers of inflammatory cells were gathered; muscle tissue lost its normal texture and structure; and the internal elastic membrane was integrated. Compared with the preoperative status, HIF-1α expression increased significantly in all subgroups (P < 0.05); there was no change in the sham group. HIF-1α expression in each subgroup was different (F = 14.267, P < 0.05). Femoral artery injection of lauric acid can be used as a rat TO model owing to its simple application and success rate. HIF-1α expression increased in the early stage of TO and gradually decreased with the extension of ischemia time; it may play a leading role in TO development and can be used for diagnosis and cure evaluation.

Integrated treatment for lower-limb stage II thromboangiitis obliterans by interventional therapy and oral administration of Chinese medicine: a randomized controlled clinical trial.

METHODS: Ninety lower-limb stage II or worse TAO patients were randomly divided into three groups: group A (30 cases) treated by intervention and oral administration of Chinese medicine; group B (30 cases) treated by intervention alone; and group C (30 cases) treated only with oral administration of Chinese medicine. Therapeutic effects were observed, including the cure rate; the recurrence rate after one month, three months, six months, nine months, and one year; the ankle brachial indexes; the incidence of complications; and the level of C-reactive protein and erythrocyte sedimentation rate. RESULTS: Group A had significantly better clinically curative effects, related indexes, and outcomes during the long-term follow-up survey, than that of groups B and C. CONCLUSION: Integrated treatment is more effective for treating lower-limb stage II or worse TAO. OBJECTIVE: To observe if integrated treatment is better than other therapies for lower-limb stage II thromboangiitis obliterans (TAO).

Thromboangiitis obliterans - case report.

Thromboangiitis obliterans (Buerger'€™s disease) represents an inflammatory disease of limbs'€™ small arteries and veins causing vascular thrombosis, and partial or total obstruction. It affects mostly male gender aged 40 years old. The peculiarity of our case is underlined by presenting a 62 years, chronic tobacco user and not compliant female patient known with thromb oangiitisobliterans for almost 15 years. The arteriographic and clinical features with concomitant and sever affected upper and lower limbs are highly suggestive, emphasizing the possibility of Buerger'€™s disease development even in female patients.

Endarteritis obliterans in the pathogenesis of Buerger's disease from the pathological and immunohistochemical points of view.

Buerger's disease (thromboangiitis obliterans) is considered to be a nonatherosclerotic, inflammatory, and vaso-occlusive disease, although the details of the mechanisms of pathogenesis remain unknown. The occurrence of the disease is strongly related to tobacco abuse and its progression is closely linked to continued smoking. The purpose of this review article is to demonstrate the pathological characteristics of arteries affected with Buerger's disease from a possible immunoreactive point of view. In addition, we present the mechanisms for preserving the architecture of the arterial wall in affected vasculatures. Thereafter, we discuss the possibility that the pathogenesis of Buerger's disease is a type of endarteritis obliterans, deeply connected to the Notch pathway, distinct from arteriosclerosis obliterans and other vasculitides.

A disease-specific activity score for Thromboangiitis obliterans.

INTRODUCTION: The aim of this study was to find a disease-specific activity score for Thromboangiitis obliterans (TAO). METHODS: About 173 admission records from 125 patients with TAO over the period 2005-2011 were evaluated. The outcome of the patients was categorized as saved-limb or limb-loss. The risk of limb loss associated with each clinical sign or symptom and complete blood count (CBC) data were then assessed. This risk assessment value was multiplied by 100 to obtain the percentage risk, which was then considered to be the risk score. The receiver operating characteristic (ROC) curve was used for demonstrating cut-offs for each score. The reliability of the risk score was evaluated using a split-half reliability test. The divergent validity of the risk score was tested using the Pearson correlation coefficient between the total scores of the patients with and without limb loss. RESULTS: The maximum possible clinical and CBC scores were 221 and 180, respectively, giving a maximum total score of 401. The cut-offs for clinical, laboratory and total score were 115, 75 and 213, respectively. CONCLUSION: Further cohort studies for evaluating the efficacy of different treatments for limb salvage of TAO patients based on these score are suggested.

Embolus-carried vascular endothelial cell growth factor 165 improves angiogenesis in thromboangiitis obliterans.

We investigated neovasculization effects of embolus-carried human vascular endothelial cell growth factor 165 (VEGF165)-encoded adenovirus (Ad) vector in the hindlimbs of rats with thromboangiitis obliterans (TAO). Rats were equally divided into blank control (I), TAO model (II), embolus (III), Ad-VEGF165 intravascular treatment (IV), Ad-VEGF165 intramuscular treatment (V), and embolus-carried Ad-VEGF165 (VI) groups. After interventional treatment, the neovasculization effect of the test gene was observed using immunohistochemistry. At 1 week after administration, compared with group II, groups V and VI had significantly increased microvessel densities, but no significant difference was observed between groups V and VI. At 2 weeks, groups V and VI exhibited significantly increased microvessel densities. At 1 week after administration, compared with group II, both groups V and VI showed a significant difference in the ratio between the α-smooth muscle actin count and the muscle fiber count, whereas no significant difference was observed between them. At 2 weeks, groups V and VI also exhibited significant differences in these ratios compared with the other groups. We conclude that Ad-VEGF165 promotes neovasculization in ischemic limbs. Embolus-carried Ad- VEGF165 had the most pronounced effect.

Clinical, arteriographic and histopathologic analysis of 13 patients with thromboangiitis obliterans and coronary involvement.

Smoking is a risk factor for thromboangiitis obliterans (TAO, Buerger's disease) and arteriosclerosis, but there are few cases of coronary heart disease (CAD)-associated Buerger's disease. A literature search for articles in English, Spanish and French published between 1966 and 2012 on patients with coronary involvement and TAO revealed 12 patients. We describe an additional case with involvement of the central nervous system, myocardium and large-diameter proximal arteries. The main clinical manifestations in these 13 cases were lower limb claudication and acute thoracic pain. The histologic findings showed thrombosis with unbroken internal elastic lamina and intimal clusters of granulocytes; coronary angiography revealed predominant involvement of the left anterior descending and right coronary artery. Treatment included coronary bypass procedures, coronary angiopiasty, smoking cessation, and anticoagulant therapy. A complete therapeutic response was observed in half the patients. This review of all published cases of TAO patients with coronary symptoms, together with our patient, demonstrates the rarity of this clinical association. Patients under age 40 with CAD but no prominent cardiovascular risk factors besides smoking should be evaluated for the presence of Buerger's disease.

Identification of S100A8/A9 involved in thromboangiitis obliterans development using tandem mass tags-labeled quantitative proteomics analysis.

Thromboangiitis obliterans (TAO) is characterized by inflammation and obstruction of small-and medium-sized distal arteries, with limited pharmacotherapies and surgical interventions. The precise pathogenesis of TAO remains elusive. By utilizing the technology of tandem mass tags (TMT) for quantitative proteomics and leveraging bioinformatics tools, a comparative analysis of protein profiles was conducted between normal and TAO rats to identify key proteins driving TAO development. The results unveiled 1385 differentially expressed proteins (DEPs) in the TAO compared with the normal group-comprising 365 proteins with upregulated expression and 1020 proteins with downregulated expression. Function annotation through gene ontology indicated these DEPs mainly involved in cell adhesion, positive regulation of cell migration, and cytosol. The principal signaling pathways involved regulation of the actin cytoskeleton, vascular smooth contraction, and focal adhesion. The roles of these DEPs and associated signaling pathways serve as a fundamental framework for comprehending the mechanisms underpinning the onset and progression of TAO. Furthermore, we conducted a comprehensive evaluation of the effects of S100A8/A9 and its inhibitor, paquinimod, on smooth muscle cells (SMCs) and in TAO rats. We observed that paquinimod reduces SMCs proliferation and migration, promotes phenotype switching and alleviates vascular stenosis in TAO rats. In conclusion, our study revealed that the early activation of S100A8/A9 in the femoral artery is implicated in TAO development, targeting S100A8/A9 signaling may provide a novel approach for TAO prevention and treatment.

Reduced circulating endothelial progenitor cells in thromboangiitis obliterans (Buerger's disease).

To determine the role of endothelial progenitor cells (EPCs) in the pathogenesis of thromboangiitis obliterans (TAO), EPC numbers and colony-forming units, migratory function and tubular structure formation in vitro were compared between 13 young male TAO patients and two age-matched healthy control groups: 11 smokers and 12 non-smokers. TAO patients had significantly lower numbers of EPCs and EPC colonies compared to both non-smokers [190 (97.0-229) vs 528 (380-556), p < 0.001 for EPCs and 0.80 (0.53-1.00) vs 2.80 (2.08-4.00) per mm(2), p = 0.001 for EPC colonies] and smokers [190 (97.0-229) vs 272 (229-326), p = 0.012 for EPCs and 0.80 (0.53-1.00) vs 2.80 (1.80-3.93) per mm(2), p = 0.001 for EPC colonies]. However, there were no significant differences in migratory function or tube formation between the three groups. These results suggest that TAO patients have an intrinsic decrease in EPCs not entirely associated with smoking, which may be the cause of endothelial dysfunction seen in TAO patients leading to the development of this disease at early ages.

Recent advances of oxidative stress in thromboangiitis obliterans: biomolecular mechanisms, biomarkers, sources and clinical applications.

Oxidative stress (OS) has been identified as a key factor in the development of Thromboangiitis Obliterans (TAO). The detection of OS levels in clinical and scientific research practice is mainly based on the measurement of oxidative stress such as reactive oxygen species (ROS), reactive nitrogen species (RNS) and lipid peroxides. These markers are typically assessed through a combination of physical and chemical methods. Smoking is known to the state of OS in TAO, and OS levels are significantly increased in smokers due to inadequate antioxidant protection, which leads to the expression of apoptotic proteins and subsequent cell injury, thrombosis and limb ischemia. There, understanding the role of OS in the pathogenesis of TAO may provide insights into the etiology of TAO and a basis for its prevention and treatment.

Buerger disease (thromboangiitis obliterans): a clinical diagnosis.

Thromboangiitis obliterans, or Buerger disease, is a debilitating vascular disease with a well-known pronounced link to cigarette smoking and, more specifically, to the nicotine component of tobacco inhalation. Buerger disease is an inflammatory occlusive disorder that primarily affects the medium and small vessels of the extremities. In the present case report, a 46-year-old man, nonforthcoming smoker, presented to the authors' clinic with a deep ulcer at the head of the second metatarsal. Evidently, although the patient continued to smoke, the ulcer responded to therapy but regressed. Once the history was elaborated, the patient stopped smoking, and the ulcer healed completely within 2 months. Follow-up appointments proved to be unremarkable and to the authors' knowledge, there has not been a reoccurrence, and the patient remains tobacco-free.

Establishment of culturing system for ex-vivo expansion of angiogenic immature erythroid cells, and its application for treatment of patients with chronic severe lower limb ischemia.

Angiogenesis therapy by bone marrow-mononuclear cell implantation (BMI) has been utilized. We found that erythroid cells played an essential role in angiogenesis by BMI. We then tried to establish a novel cell therapy by implantation of ex vivo expanded immature erythroblasts cultured from hematopoietic stem/precursor cells. Immature to mature erythroblasts were purified from human bone marrow, and mRNA expression were analyzed. Strongly expressed VEGF and PLGF in immature erythroid cells decreased according to erythroid maturation. To expand very immature erythroid cells, we established a two-step culturing system, i.e., bone marrow cells were cultured in the presence of Flt-3L, SCF and TPO for 7 days, and the cells were further cultured in the presence of SCF, IGF-I and EPO for an additional 7 days. The in vivo angiogenic effects of implantation of the ex vivo expanded cells were stronger than that of BMI in mouse limb ischemia model. Three patients with severe chronic lower limb ischemia accompanied by Burger's disease or collagen arteritis were enrolled in a pilot clinical trial of the novel cell therapy by transplantation of ex-vivo expanded immature erythroid cells. In the clinical trial, most clinical symptoms such as rest pain and skin ulcers improved in 4 weeks, and did not recur in the one-year follow-up. No adverse events were observed in any of the patients. Moreover this novel cell therapy required only a small amount of bone marrow collection. Further enrollment of patients with chronic severe lower limb ischemia is necessary to confirm the efficacy and safety of this novel cell therapy, and to estimate the necessary amount of bone marrow aspirate.

Classification of corkscrew collaterals in thromboangiitis obliterans (Buerger's disease): relationship between corkscrew type and prevalence of ischemic ulcers.

BACKGROUND: A corkscrew collateral appearance on angiography is one of the diagnostic criteria for Buerger's disease. The purpose of the present study was to classify the angiographic findings of corkscrew collaterals and to evaluate the relationship between corkscrew collateral type and the severity of Buerger's disease. METHODS AND RESULTS: Corkscrew collaterals were assessed on digital subtraction angiography in lower extremities of 28 patients with Buerger's disease (55 limbs). The corkscrew sign was classified into 4 types by size and pattern as follows: type I, artery diameter >2 mm, large helical sign; type II, diameter >1.5 mm and or=1 mm and

MiR-223 alleviates thrombus and inflammation in thromboangiitis obliterans rats by regulating NLRP3.

OBJECTIVE: The aim of this study was to observe the regulatory effects of micro ribonucleic acid (miR)-223 on thromboangiitis obliterans (TAO) rats, and to explore the potential regulatory mechanism. MATERIALS AND METHODS: Online database TargetScan was used to predict the downstream regulatory targets of miR-223. A total of 45 Sprague Dawley (SD) rats were randomly divided into three groups, including sham operation group (Sham group), Model group, and miR-223 agonist group (miR-223 mimic group). TAO model was successfully established in rats through the injection of lauric acid via the femoral artery. The content of serum thromboxane B2 (TXB2) and endothelin (ET) was measured via enzyme-linked immunosorbent assay (ELISA). The pathological changes in the left hind limb were detected via hematoxylin-eosin (HE) staining. Moreover, the expressions of interleukin-6 (IL-6) and IL-1ß in the tissues of the rat left hind limb were determined via immunohistochemistry. In addition, the protein expression of Nod-like receptor protein 3 (NLRP3) in tissues was determined using Western blotting. RESULTS: TargetScan database predicted that NLRP3 was the downstream target gene of miR-223. Compared with the Sham group, Model group exerted significantly higher content of serum TXB2 and ET, severe lesions in the rat left hind limb, as well as significantly increased expressions of IL-6 and IL-1ß and protein expression of NLRP3 in tissues of the rat left hind limb (p<0.05). Besides, compared with the Model group, miR-223 mimic group showed remarkably lower content of serum TXB2 and ET, improved lesions in the rat left hind limb, as well as decreased expressions of IL-6 and IL-1ß and protein expression of NLRP3 in the tissues of the rat left hind limb (p<0.05). CONCLUSIONS: MiR-223 agonist can alleviate thrombus and inflammatory response in TAO rats. The possible underlying mechanism may be related to targeted regulation on NLRP3 inflammasome expression.