Small Vessel Involvement Research Articles

Child Neurology: Aicardi-Goutières Syndrome Presenting as Recurrent Ischemic Stroke

Aicardi-Goutières syndrome (AGS) is a rare, single-gene disorder, characterized by neurologic and skin involvement with an increased level of interferon-α (IFN-α) in the CSF. We describe the case of a young patient presenting with recurrent ischemic stroke. Evaluation revealed the presence of chilblains, white matter abnormalities, cerebral atrophy, and raised IFN-α in the CSF. Compound heterozygous variants of TREX1 were detected, confirming a diagnosis of AGS. After excluding other causes, we attributed the stroke to AGS. Tofacitinib, a Janus kinase inhibitor, was administered to our patient in addition to antiplatelet drugs. There was no recurrence of stroke during 3-month follow-up. This is a rare case of recurrent stroke in TREX1-mutated AGS. Small vessel involvement has been previously demonstrated to play a significant role in the pathogenesis of AGS. This microvascular mechanism might explain the occurrence of ischemic stroke in our patient. For young patients with stroke and multiple system involvement, genetic disorders including AGS should be considered.

Long-Term Prognostic Factors in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A 15-Year Multicenter Retrospective Study.

BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients.Materials and MethodsA multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results.ResultsIn the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676–0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model.ConclusionLaboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.

Whether Behçet’s patients with large vessel involvement have concurrent small vessel involvement? A case-control Study

Behçet’s disease (BD) is a chronic multisystem disorder with the principal pathological finding of vasculitis, which may involve vessels of different sizes. The concurrence of small and large vessel involvement in BD patients is undetermined. The current study aims to evaluate small vessel involvement in BD patients with large vessel involvement. The study population comprised 35 BD patients with large vessel involvement (cases) and 35 BD patients without large vessel involvement (controls). Small vessel involvement was evaluated in all patients by capillaroscopy. Capillaroscopic findings were compared between the two groups. According to the capillaroscopic findings, all of our BD patients had small vessel involvement. The most prevalent abnormality was tortuosity (87.1%), followed by enlarged loops (58.6%) and avascular areas (51.4%). Capillaroscopy findings between the case and the control groups were not statistically different. There was a significant association between microbleeding and history of erythema nodosum (P-value = 0.015), tortuosity and a history of skin aphthosis (P-value = 0.015), architectural derangement and history of uveitis (P-Value = 0.029), the number of avascular areas and active oral aphthosis (P-value = 0.021), and architectural derangement and increased ESR (P-value = 0.011). There was no difference in nail fold folder involvement between BD patients with and without large vessel involvement; however, some capillaroscopic features were associated with some disease manifestations.

ECMO Rescues Patients With Acute Respiratory Failure Related to GPA.

Granulomatosis with polyangiitis (GPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis with a wide range of clinical symptoms related to the systemic involvement of small blood vessels. The respiratory system is one of the most frequently involved, and life-threatening acute respiratory failure could occur due to diffusive alveolar hemorrhage and tracheal stenosis. When maximum mechanical ventilation is unable to maintain oxygenation, extracorporeal membrane oxygenation (ECMO) should be considered as the final respiratory supportive method, if available. Here we present a 32-year-old male patient with acute respiratory failure (ARF) related to GPA, who was rescued by winning time for accurate diagnosis and appropriate treatment. Additionally, we reviewed more than 60 GPA-related ARF cases on multiple online databases, summarized the clinical manifestations of these patients, and concluded that ECMO plays an important role in further respiratory support for ARF patients with GPA and assists in accurate and timely diagnosis and appropriate treatment, thus helping them recuperate.

Peripheral retinal arteriolar leakage in giant cell arteritis: a case report

A 76-year old African American female with a history of arteritic ischemic optic neuropathy (AION) secondary to biopsy-proven giant cell arteritis (GCA) presented with unilateral vision loss in her contralateral eye despite high-dose oral steroid treatment. Dilated fundus examination revealed three cotton wool spots. Fluorescein angiography showed slowed arteriolar filling with late staining of small peripheral arteries, consistent with small vessel arteritis. Laboratory tests for alternative vasculitides were negative. Review of her temporal artery biopsy specimen confirmed lymphoplasmacytic inflammation around small adventitial vessels with no destructive granulomatous or leukocytoclastic small vessel vasculitis, consistent with GCA. Our unique case demonstrates peripheral small vessel retinal arteriolar leakage in GCA, which is a rare finding. This association is of interest because GCA is commonly associated with medium to large vessel pathology without small vessel involvement.

Primary CNS vasculitis: A systematic review on clinical characteristics associated with abnormal biopsy and angiography.

Primary Central Nervous System Vasculitis (PCNSV) remains a diagnostic challenge due to its variable and non-specific clinical manifestations. In part, the clinical heterogeneity of PCNSV may be a consequence of the modalities used for diagnosis; accordingly, there may be different subtypes of PCNSV based on whether the diagnosis was attained by biopsy or cerebral angiography. To examine the frequency of symptoms, laboratory, and radiological features associated with PCNSV, and to identify distinct clinical features between biopsy and angiography defined PCNSV. We conducted a systematic review of articles published in the English language from 1991 to 2019 that met all diagnostic criteria of PCNSV. We identified 55 studies, reporting on 907 PCNSV cases. Median age was 45 (IQR 50-36), and 53% were women. Biopsy compared to angiography defined PCNSV had a higher percentage of cognitive impairment, and seizures on initial presentation, and were more likely to have a subacute or progressive onset, abnormal CSF profile, small vessel involvement on angiography, and tumor-like lesions and gadolinium enhancement on MRI. Angiography defined PCNSV were more likely to have an acute onset, focal weakness and visual impairment on initial presentation, medium vessel involvement on angiography, and infarcts on MRI. Brain biopsy was diagnostic of PCNSV in 71% of cases, and demonstrated an alternative diagnosis in 37% of cases, the most common being infection (19%) and lymphoproliferative disease (18%). This study provides further evidence that there are distinct clinical features between biopsy and angiography defined PCNSV, which may aid in selecting patients for appropriate invasive tests.

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series.

Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Multisystemic manifestations of IgA vasculitis.

Immunoglobulin A vasculitis (IgAV), also known as Henoch-Schönlein Purpura, is one of the most common kind of systemic vasculitis in children, and due to the involvement of small blood vessels throughout the body, this disease can cause a variety of symptoms in different organs. Our aim was to review the data on various systemic manifestations of IgAV. A research of the literature was performed in PubMed database, utilizing the MeSH terms "IgA vasculitis" and "Henoch Schönlein Purpura". According to the predetermined structure of the manuscript, we extracted and sorted out the relevant data. Clinically, almost all the patients will present with palpable skin purpura, together with arthritis, gastrointestinal tract involvement, or kidney damage. Other rare systemic manifestations include neurological symptoms, scrotal involvement, and cardiopulmonary disease. When uncommon complications occur, patients may be misdiagnosed as other diseases, thus delaying treatment. Although the course of IgAV is mostly self-limited, misdiagnosis can also lead to a poor prognosis. A comprehensive awareness to the clinical manifestations of IgAV is the necessary prerequisite for its timely diagnosis. Prompt diagnosis and adequate treatment are essential for optimal results.

Cutaneous Vasculitis: Review on Diagnosis and Clinicopathologic Correlations.

Cutaneous vasculitis is an inflammatory disease affecting the dermal blood vessel walls. The skin is a privileged organ in the setting of vasculitis since it is easily accessible for physical examination and safe biopsy, allowing an accurate characterization of inflammatory lesions. The skin is often involved. Also, cutaneous vasculitis can reflect a cutaneous component of a systemic vasculitis, a skin-limited or skin-dominant expression or variant of a systemic vasculitis, or be a single-organ vasculitis per se. Vasculitis lesions are multiple and polymorphic. They may induce a wide spectrum of clinical manifestations depending on the location and the size of the vessels involved. The depth of affected vessels is correlated with the type of cutaneous lesions. Involvement of small superficial vessels results mostly in urticarial, but relatively persistent plaques, papules, and palpable purpura. Involvement of vessels in the dermohypodermic junction or hypodermis results in ulcers, nodules, or livedo. The type of inflammatory infiltrate is also a key finding for the diagnosis of cutaneous vasculitis. Leukocytoclastic vasculitis is not a disease per se but the result of a pathophysiological process common to different causes. A better knowledge of the vascular anatomy of the skin, elementary lesions, and histological characteristics of dermatologic manifestations would allow a more relevant and more efficient diagnostic approach. We also propose a list of additional exams to be performed in front of skin lesions suggestive of vasculitis. The aim of our article is to provide an overview of elementary skin lesions and clinicopathologic correlations in cutaneous and systemic vasculitis.

1929 Spots and Dots on the Skin and Stomach: Gastrointestinal Vasculitis

INTRODUCTION: Immunoglobulin A (IgA) vasculitis is often seen in the pediatric population but can also be seen in the adult cohort. The classic histopathological finding in IgA vasculitis is leukocytoclastic vasculitis (LCV), which is a neutrophilic inflammation in post-capillary venules. Classic signs of LCV include palpable purpura, small vessel involvement, and less likely but also extracutaneous manifestations. We present a unique case of a gastrointestinal (GI) manifestation of LCV with angiodysplasia in the stomach and duodenum. CASE DESCRIPTION/METHODS: This is a 66-year-old female with a history of hypertension, chronic kidney disease stage III, hypothyroidism, a recent diagnosis of LCV (Figure 1) two weeks prior that returns to the hospital with a complaint of watery diarrhea, bright red blood per rectum, lower abdominal cramping, and nausea. Her vitals were unremarkable and her laboratory studies revealed elevated blood urea nitrogen (BUN), acute kidney injury, mild anemia, and leukocytosis. A computed tomography (CT) scan of her abdomen demonstrated extensive wall thickening, multifocal periduodenal inflammation, and diffuse ileal wall thickening (Figure 2). An esophagogastroduodenoscopy (EGD) revealed ulcerative esophagitis, helicobacter pylori negative duodenal ulcers, and multiple non bleeding angiodysplasias in the stomach and duodenum that were cauterized (Figure 3). A colonoscopy revealed a tubular adenomatous polyp that was removed. The patient’s symptoms resolved and she did not demonstrate any further bleeding. Her hemoglobin stabilized and she was able to tolerate a regular diet on discharge. DISCUSSION: Abdominal pain and bloody diarrhea can have a milieu of differentials. This patient clearly demonstrated a vasculitic GI manifestations with bowel wall thickening and inflammation on imaging, elevated BUN, anemia, bloody diarrhea, and a history of LCV. Having a proper suspicion and confirming this with imaging, endoscopy, and biopsy is imperative for the diagnosis. Without a thorough history and physical, undiagnosed vasculitis can lead to fatal consequences such as gastrointestinal hemorrhage, perforation, or more rarely infarction.

31. Takayasu arteritis presenting as bilateral popliteal artery aneurysm: a rare presentation of a rare disease

IntroductionTakayasu arteritis (TA) is a rare, yet well recognised, chronic granulomatous arteritis that mostly affects large vessels in those below 50 years of age. According to the 2012 Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitides, Takayasu arteritis is classified as large vessel vasculitis as it mainly affects the aorta and its major branches. However, our patient is outside the norm as he has biopsy-proven Takayasu arteritis with no or little involvement of the aorta. Instead, he presented with bilateral popliteal artery aneurysm.Case descriptionThe patient is a healthy Yemeni gentleman. In 2011 (26-years-old), he started to complain of multiple joint pain and swelling associated with morning stiffness which was relieved after taking some medications. Incidentally, he was found to have high blood pressure which was not investigated as he was lost to follow-up.In 2016 (31-years-old), his symptoms recurred. He was diagnosed to have seronegative rheumatoid arthritis and started on csDMARDs, but he stopped them, and he was lost follow-up again.In July 2018 (33-years-old), he presented with complaints of painful swelling at the back of his right knee for around one month. The swelling was found to be a pulsatile mass and ultrasound was suggestive of popliteal artery aneurysm. CT angiography of lower limbs confirmed the presence of bilateral popliteal artery aneurysm. He underwent excision of the right aneurysm with vein interposition graft and rheumatology team was consulted.Apart from polyarthritis and hypertension, he denied any symptoms related to connective tissue diseases or vasculitides. He does not smoke. He was born to consanguineous parents but no family history of rheumatic or hereditary collagen disorders. He has normal body habitus, normal skin turgor, intact peripheral pulses and no evidence of synovitis.His laboratory workup revealed normal blood count, biochemistry panel and urinary studies but raised inflammatory markers. All serology and autoimmune workup came back negative. CT angiography of brain, chest and abdomen showed aortic ectasia with stenotic lesions in renal arteries. Biopsy of the resected aneurysm showed chronic inflammation with giant cells infiltrate compatible with TA.He was treated with steroids and intravenous cyclophosphamide pulse therapy for 6 months and then maintained on methotrexate. He is scheduled for angioplasty of the renal arteries.DiscussionDespite being considered a rare disease, Takayasu arteritis has been described in many parts of the Arab world. According to a 2014 systematic review by K Mustafa, the epidemiological and clinical features of TA in Arabs were similar to different parts of the world. However, this patient is unique in several ways. He presented mainly with episodes of inflammatory polyarthritis of large and small joints which was diagnosed as rheumatoid arthritis, because he did not have the usual constitutional symptoms (fever, weight loss, fatigue, and arthralgia) that are characteristic of the inflammatory phase of TA. The only clue that could have been used to point towards vasculitis as a cause of his symptoms was the overlooked high blood pressure which affects between 33–83% of patients with TA; reflecting the common involvement of the main renal arteries in TA. Hence, the delay in the diagnosis which is also a common finding in reported cases of TA worldwide. Most angiographic studies done to show the pattern of vascular involvement in TA showed that the thoracoabdominal aorta was the most common vessel involved, followed by the subclavian vessels with some differences between Japanese and Indian populations. However, many reported cases demonstrated the involvement of medium and small size vessels as well. CT angiogram of the patient did not convince us of any aortic involvement. However, there was stenotic lesions involving the renal arteries and aneurysmal dilatation of both popliteal arteries. This pattern of involvement that spared the aorta and its major branches raised the question of other types of vasculitides such as Behçet’s disease and polyarteritis nodosa, which made us treat him with intravenous cyclophosphamide initially. However, the clinical presentation and the biopsy supported the diagnosis of Takayasu arteritis rather than other vasculitides, so we have decided to maintain the patient on methotrexate.Key learning pointsPatients presenting with symmetric polyarthritis should be assessed thoroughly before labelling them as rheumatoid arthritis, especially if they are seronegative in order to not miss other important differential diagnoses such as in this case the diagnosis of vasculitis. Paying attention to other associated symptoms such as dermatologic or eyes manifestations or hypertension, can help in pointing towards other important differentials. Hypertension is an important and common manifestation of the vasculitides and can be the only presenting feature to unmask the presence of vasculitides. Therefore, vasculitides should be kept in the differential diagnosis of patients with secondary hypertension. TA is a disease of the aorta and its major branches. However, it can in rare situations affect other vessels and can present without involvement of the aorta. Conflicts of interestThe authors have declared no conflicts of interest.

HENOCH-SCHONLEIN PURPURA IN CHILDREN: A CROSS SECTIONAL STUDY

Background: Henoch-Schonlein purpura (HSP) is a leukocytoclastic vasculitis with small vessel involvement and mainly affects the skin as well as joints, the gastrointestinal system (GIS), kidneys, and, more rarely, other organs. Objective: The objective of this study was to evaluate the sociodemographic characteristics, and clinical and laboratory findings of patients diagnosed with HSP. Materials and Methods: This was a retrospective study done to find out the sociodemographic data, clinical, laboratory findings, and treatment information of patients diagnosed with HSP and was admitted to the Pediatric Clinic of a tertiary care hospital between January 1, 2008, and August 31, 2013. The data were obtained from the hospital’s data processing system. HSP cases were validated according to EULAR/PRINTO/PRES criteria. Mean standard deviation, median, lowest and highest, frequency, and ratio values were used in the descriptive statistics of the data. Results: The study included 85 patients between the ages of 2 and 16 years, wherein 49 patients (57.6%) were male and 36 (42.4%) were female. The mean age was 9.9±3.3 years and 53 patients (62.4%) were under 10 years of age. The most common precipitating factor was upper respiratory tract infections. Purpura was the only symptom observed in all the patients and joint involvement was the second most common symptom (60%). GIS involvement was observed in 46 patients (58.8%) and intussusception was observed in one patient. Nine patients (10.6%) had renal involvement with mild nephropathy. The most frequently observed laboratory findings were increased C-reactive protein (47%) and leukocytosis (31%). Conclusion: HSP is commonly seen in children and leads to life-threatening complications in a minority of patients. Whole patients with GIS and renal involvement should be examined and monitored to assess the severity of the disease and any complications.

Imaging in small and medium vessel vasculitis.

Vasculitis includes a group of disorders characterized by inflammation of the vessel wall and classified based on the diameter of the predominantly involved vessels. Granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis and Henoch-Schonlein purpura are the important entities in the small vessel vasculitis group, while polyarteritis nodosa and Kawasaki disease represent the medium vessel vasculitis group. The clinical manifestations may be non-specific and there may be considerable overlap with the other disorders. Imaging plays an important role in diagnosis as well as the management of patients with small and medium vessel vasculitis. Imaging allows direct evaluation of the arteries in medium vessel vasculitis. However, the involved vessels in small vessel vasculitis are smaller than the resolution of the current imaging techniques. Hence, only the end organ changes secondary to involvement of small vessels are examined. In this review we discuss the role of current imaging modalities (predominantly computed tomography and magnetic resonance imaging) as well as individual disease entities in the groups of small and medium vessel vasculitis.

Vasculitis in Systemic Autoinflammatory Diseases.

Autoinflammatory diseases (AID) are diseases of the innate immune system, characterized by recurrent episodes of localized or systemic inflammation. Vasculitis may accompany AID. The causes of the association of vasculitis with monogenic AID are still debated. Among the monogenic AID, Familial Mediterranean Fever (FMF) is the most common. IgA-related vasculitis (IgAV) and Polyarteritis Nodosa (PAN) involving small and/or medium-sized vessels have an increased frequency among FMF patients. There are also case reports revealing vasculitic features in Cryopyrin-Associated Periodic Fever Syndrome (CAPS), Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Mevalonate Kinase Deficiency (MKD), also known as Hyper IgD syndrome (HIDS), Deficiency of IL-1 Receptor Antagonist (DIRA) and Pyogenic Arthritis, Pyoderma gangrenosum, and Acne (PAPA) patients. Central nervous system vasculitis and vasculopathy have been reported in DIRA and PAPA patients whereas small vessel involvement affecting skin has been reported in CAPS, TRAPS, and MKD patients. Alternatively, vasculitis can also be a leading feature especially in the recently defined monogenic AID (Otulipenia, Deficiency of Adenosine Deaminase 2-DADA2, Haploinsufficiency of A20) and interferonopathies (STING-associated vasculopathy with onset in infancy-SAVI). DADA2 often presents as a PAN-like disease. In otulipenia, patients have painful subcutaneous nodules caused by septal panniculitis with small and medium vessel vasculitis. Haploinsufficiency of A20 (also called Familial Behcet-like Autoinflammatory Syndrome) results in a phenotype very similar to the variable vessel vasculitis of Behcet's disease with recurrent oral-genital ulcers, in addition to, skin rash, uveitis, and polyarthritis. SAVI is an autoinflammatory vasculopathy with increased Interferon (IFN) signature, causing severe skin lesions resulting in ulceration, necrosis, and in some cases, amputation. Behcet's Disease (BD) is a multifactorial polygenic AID characterized by recurrent attacks of oral-genital ulcers, skin lesions, uveitis and a unique vasculitis affecting both arteries and veins of all sizes. Many clinical features overlap with other autoinflammatory diseases and overexpression of proinflammatory cytokines is an important feature of the disease.

Clinical Characteristics and Outcomes in Asian Patients With Premature Coronary Artery Disease: Insight From the FOCUS Registry.

Premature coronary artery disease (PCAD) is increasingly common in Asian countries; however, less is known regarding its characteristics and clinical outcomes. This study aims to describe clinical characteristics and investigate clinical outcomes in real-world Asian patients with PCAD. A total of 4700 Asian patients undergoing drug-eluting stent implantation were included in our study and divided into PCAD group and mature CAD (MCAD) group according to their onset age. All patients were followed up for 3 years to observe their clinical outcomes. Patients with PCAD were more likely to be associated with acute coronary syndrome (ACS; P = .03) and acute occlusive lesion ( P < .001). Reference diameter ( P < .001) and lesion diameter stenosis ( P = .001) were significantly greater in PCAD group. Conversely, the MCAD group was more likely to be associated with left main disease, severe calcification lesion and small vessel involvement. The cumulative incidences of major adverse cardiovascular event (MACE; P = .007), cardiovascular death ( P < .001), and all cause death ( P < .001) were significantly lower in PCAD group than those in MCAD group. Although more often manifested as ACS, PCAD is associated with lower risks of MACE and cardiovascular death than MCAD in real-world Asian population.

Angiographic evidence of small vessel involvement in Fabry disease

Angiographic evidence of small vessel involvement in Fabry disease

THROMBOTIC AND THROMBOEMBOLIC COMPLICATIONS IN SYSTEMIC VASCULITIS

Nowadays, there is no doubt about the relationship between immune inflammation and the development of thrombosis due to the similarity of many pathogenetic machanisms underlying both pathological processes. Systemic vasculitis, along with other immuno- mediated inflammatory diseases, represent one of the most clear examples of such interaction. Thrombotic complications remain one of the most serious and life-threatening conditions that occur in patients with autoimmune diseases, in particular systemic vasculitis. This serves as powerful stimulus for studing the problem of hypercoagulation, which often accompanies the course of systemic vasculitis. Of interest are thrombosis that occure both in the injury of large vessel and in the involvement of medium and small vessels in the pathological process. According to the literature, thrombotic and thromboembolic complications are most common in ANCA-associated vasculitis and Behçet’s disease. This review discusses current studies regarding features of clinical picture and mechanisms of thrombosis development in systemic vasculitis. Because of these studies it became clear that for some vasculitis a high frequency of both arterial and venous thrombosis is characteristic. At the same time, other vasculitis are accompanied by high risk of only venous thrombosis. Finally, thrombosis and thromboembolism are quite rare complications for some vasculitis. Among the presented mechanisms of thrombosis involvement, disruptions of the hemostasis are widely considered. For examples, the presents the results of researches, which is actively discussed the role of neutrophil extracellular traps and antiendothelial cell antibodies in the development on thrombotic complictions. Special attention is paid to the possible role of some disorders of hemostasis, such as polymorphism V coagulation factor G1691FA and prothrombin G20210A. To search for literature sources, the following queries were used: “vasculitis”, “thrombosis”, “neutrophil extracellular traps”, “ANCA-associated vasculitis”, “venous thrombosis”, “arterial thrombosis”, “Behçet’s disease”, “Takayasu arteritis”, “granulomatosis with polyangiitis”, “eosinophilic granulomatosis with polyangiitis”, “Mmicroscopic polyangiitis”, “Henoch–Schönlein purpura”, “Kawasaki disease”, “polyarteritis nodosa”, “giant cell arteritis”, “Buerger’s disease”. In addition, use similar requests in English. The search was carried out in PubMed.

MINERAL'NAYa PLOTNOST' KOSTI I SOSTOYaNIE SOSUDISTOY STENKI V ZAVISIMOSTI OT STATUSA REPLIKATIVNOGO KLETOChNOGO STARENIYa U ZhENShchIN V POSTMENOPAUZAL'NOM PERIODE

Objective: to examine the relationship between bone mineral density (BMD), the parameters of vascular stiffness and biomarkers of cellular aging in postmenopausal women. Materials and Methods: In a cross-sectional study107 patients were included: women at the age range of 45 to 82 years who were observed outpatient and signed a written informed consent. Assessment of BMD was performed using DXA (Delphi W, Hologic, USA). The intima-media thickness (IMT), the presence and quantity of atherosclerotic plaques (AP), and the degree of carotid stenosis were examined by duplex scanning. The pulse wave velocity (PWV), augmentation index (Aix) were measured by applanation tonometry (SphygmoCor).To determine telomere length (DT) in leukocytes the method of real-time PCR was used. This was done by measuring the relative telomere length in the genomic DNA. Determination of telomerase activity (Aix) was carried out on pure monocyte fraction of isolated blood cells on the basis of telomerase polymerase reaction.Statistical analysis was performed using the software application Statistical Analysis System (USA). Results: With the increase in duration of menopause a gradual increase in the stiffness rate (PWV, AI), IMT and decrease of BMD was noticed in all examined parts of the skeleton. The maximal values of vascular stiffness, minimal values of BMD and the shortest telomeres were found in patients with 10+ years of menopause. The risk of bone mass loss and osteoporosis increased by 3 times in patients with high values of PWV ≥10 m/sec[OP-3,1, 95%CI, 1,13-9,89 (p&lt;0,05)], by more than 4 times in patients with AI≥ 20% [OP-4,35, 95%CI, 1,02-11,0 (p&lt;0,05)]and the IMT &gt;0,9 mm by 2,45 times in patients with presence of AP in the carotid arteries and with the shortest telomeres [OP-2,45, 95%CI, 1,05-6,08 (p&lt;0,05)]. During multivariate regression analysis after adjusting for age and menopause duration the negative relationship between IA, IMT and BMD remained highly significant, while in relation to PWV, AP presence and telomere length, such a correlation was not confirmed. Conclusion: In postmenopausal women low BMD is associated with high rates of Aix and the thickness of the IMT. The independent relationship of BMD with Aix, rather than with PWV, apparently could be explained by the involvement of small vessels -arterioles. Short telomeres are 2.45 times more frequent in patients with low bone mass, but the relationship has not been confirmed in the regression analysis, which excludes the independent nature of this aging marker with BMD.

Enhanced MRI Evaluation of Children with Sickle Cell Following Hematopoietic Stem Cell Transplantation

Introduction: Sickle cell disease (SCD) CNS vasculopathy (SCNSV) is a frequent indication for hematopoietic stem cell transplantation (HSCT). Untreated, SCNSV can be progressive and impair quality of life (QoL) and cognitive functioning. By clinical MRI/MRA assessment, HSCT is thought to halt progression of SCNSV. Quantitative analysis of T2-weighted FLAIR MRI for white matter hyperintensity (WMH) can provide a meaningful estimate of small vessel cerebrovascular burden. Adding WMH assessment, we asked whether HSCT for SCD halted long-term progression of SCNSV, including small vessel involvement, despite transplant-associated CNS risks. QoL assessment can track school functioning and physical, emotional and social functioning.Methods: This retrospective single site study compared MRI analyses pre-transplant to 1-7-years post-HSCT. Subject eligibility required availability of clinical MRI scans from within 2 months pre-HSCT and at 1-year intervals for at least one year post-HSCT. Interim scans performed for acute clinical indications were not included in the analysis. MRI scans were evaluated independent to the initial clinical read by one neuroradiologist, and via in-house developed software to quantitate WMH burden. QoL was completed by parent- and child-report pre-HSCT and annually thereafter using the Peds QL 4.0TM with scores 0-100; higher numbers reflected higher QoL.Results: 25 patients who received HSCT for SCD between 2003-2014 were evaluated. Median age at HSCT was 9.9 years (1.4-21.9); male:female 18:7; HbSS (17), HbSC (3), HbS-Bthalassemia (5). Donors were related (14) or unrelated (11). Stem cell sources were: related bone marrow (BM) (10), unrelated BM (5), related cord blood (CB) (3), unrelated CB (6), or related peripheral blood stem cells (1). Eight patients had CNS pathology as the indication for HSCT. Transplant complications were: PRES (2), stroke (1), graft failure (2), death (1). Duration of follow-up was: 1 yr (9), 2 yrs (10), >2 yrs (6). Only a minority of patients had normal pre-HSCT MRI (5) and normal MRA (11; 6 had 1-2 stenoses <2mm and were rated as ambiguous). At 1 to 7 yrs post-HSCT, 5 originally normal MRIs were unchanged, 15 MRIs were stable and 4 were improved at 1 year post-HSCT, without subsequent changes by clinical assessment. One MRI worsened due to peri-HSCT hemorrhagic stroke. MRAs were unchanged following HSCT. Preliminary analysis of 18 patients at pre-HSCT revealed that 5 did not have elevated WMH, while elevated WMH was detected in 13 patients. WMH remained stable in 16 of 18 patients over subsequent annual assessments. In the 2 patients with markedly elevated WMH pre-HSCT, values decreased at follow-up, corresponding to the resolution of acute or recent infarction. Overall pre-HSCT QoL by parent-report (N=19) was 65.3 (SD16.3); while child self-report (N=14) was 67.6, (SD13.1). After mean follow-up of 3 years, parent-report QoL improved to 78.8 (SD15.8), and self-report to 78.7 (SD15.2).Conclusions: Most children in this retrospective cohort had MRI abnormalities pre-HSCT, and all but 1 were stable or improved post-HSCT, despite PRES and other potential CNS complications. Pre-HSCT WMH appeared to be unchanged for most of these patients, while stroke-induced WMH appears to decrease over time, suggesting stable small vessel SCNSV following transplantation. Overall, by MRI/MRA and by preliminary WMH, HSCT appears to have stabilized large and small vessel SCNSV in all but 1 of 25 children. While only a modest number of patients were assessed, WMH was reproducible at multiple annual time points. Long-term parent and self-reported QoL indicated improvement from HSCT. Chronically transfused SCD patients could not be compared due to lack of annualized assessment. Future transplant protocols will include enhanced MRI-based tracking, in conjunction with QoL and neuropsychological assessments. These data could be useful for decision-making about SCD transplantation. DisclosuresNo relevant conflicts of interest to declare.

Infratentorial Microbleeds: Another Sign of Microangiopathy in Migraine.

Migraine is a risk factor for clinical stroke and for subclinical white matter hyperintensities and infratentorial infarcts. These subclinical lesions are linked to small-vessel pathology. Cerebral microbleeds (CMBs) are another biomarker of small-vessel disease but have not yet been studied in migraine. Identification of CMBs in 63 migraineurs (25 with aura/35 without aura/3 unknown aura status) and 359 controls (aged, 73-85 years) from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) magnetic resonance imaging study. We assessed the modifying role of migraine in the co-occurrence of CMBs, infarcts, and white matter hyperintensity-load. Infratentorial microbleeds were more prevalent in migraine without aura patients than controls (14% versus 4%). Prevalence of other CMBs, infarcts, and white matter hyperintensities did not differ between groups. Migraineurs with CMBs had more often infarcts than controls with CMBs (65% versus 43%). In comparison with controls with infarcts, migraineurs with infarcts had more commonly CMBs (55% versus 30%). Migraine, notably without aura, is associated with infratentorial CMBs at older age. CMBs and infarcts co-occur more often in migraine than in controls. This supports the hypothesis of small-vessel involvement in migraine pathophysiology.