Small Vessel Occlusive Disease Research Articles

Atrial Fibrillation In Patients With Stroke Attributed to Large- or Small-Vessel Disease

The STROKE AF study found that in patients with prior ischemic stroke attributed to large-artery atherosclerotic disease (LAD) or small-vessel occlusive disease (SVD), 12% developed AF over 1 year when monitored with an insertable cardiac monitor (ICM). The occurrence over subsequent years is unknown. To compare the rates of AF detection through 3 years of follow-up between an ICM vs site-specific usual care in patients with prior ischemic stroke attributed to LAD or SVD. This multicenter, randomized (1:1) clinical trial took place at 33 sites in the US with enrollment between April 2016 and July 2019 and 3-year follow-up through July 2022. Eligible patients were aged 60 years or older, or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index ischemic stroke attributed to LAD or SVD within 10 days prior to ICM insertion. Of the 496 patients enrolled, 492 were randomized and 4 were excluded. ICM monitoring vs site-specific usual care. The prespecified long-term outcome of the trial was AF detection through study follow-up (up to 3 years). AF was defined as an episode lasting more than 30 seconds, adjudicated by an expert committee. In total, 492 patients were randomized and included in the analyses (median [IQR] age, 66 [60-74] years; 307 men [62.4%] and 185 women [37.6%]), of whom 314 completed 3-year follow-up (63.8%). The incidence rate of AF at 3 years was 21.7% (46 patients) in the ICM group vs 2.4% (5 patients) in the control group (hazard ratio, 10.0; 95% CI, 4.0-25.2; P < .001). Patients with ischemic stroke attributed to LAD or SVD face an increasing risk of AF over time and most of the AF occurrences are not reliably detected by standard medical monitoring methods. One year of negative monitoring should not reassure clinicians that patients who have experienced stroke will not develop AF over the next 2 years. ClinicalTrials.gov Identifier: NCT02700945.

Differential associations between pre-diabetes, diabetes and stroke occurrence among West Africans

BackgroundThere are limited data from Africa on the burden and associations between pre-diabetes (pre-DM), diabetes mellitus (DM) and stroke occurrence in a region experiencing a profound rise in stroke burden. PurposeTo characterize the associations between stroke and dysglycemic status among West Africans. MethodsThe Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with clinical and radiological evidence of an acute stroke. Controls were age-and-gender matched stroke-free adults. Detailed evaluations for vascular factors were performed. Pre-diabetes was defined as HBA1c of 5.7%-6.4% or Fasting blood glucose (FBG) 5.6-7.0 mmol/L and DM as HBA1c >6.5% or FBG>7.0 mmol/L. We used conditional logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval. ResultsAmong 2,935 stroke cases the mean age was 60.0 ± 14.2 years with 55.2% being males. By glycemic status, 931 (31.7%) were euglycemic, 633 (21.6%) had Pre-diabetes and 1371 (46.7%) had DM. Of the age- and sex-matched stroke-free controls 69.2% were euglycemic, 13.3% had pre-DM and 17.5% had DM. Pre-DM [aOR (95% CI): 3.68(2.61-5.21)] and DM [4.29 (3.19-5.74)] were independently associated with stroke. The aOR of Pre-DM for ischemic stroke 3.06 (2.01–4.64)] was lower than 4.82 (3.37-6.89) for DM. However, the aOR of Pre-DM for hemorrhagic stroke 6.81 (95% CI: 3.29 – 14.08)] was higher than 3.36 (1.94–5.86) for DM. Furthermore, the aOR of pre-DM for ischemic stroke subtypes were 9.64 (1.30-71.57) for cardio-embolic stroke, 3.64 (1.80–7.34) for small-vessel occlusive disease and 4.63 (0.80-26.65) for large-vessel disease. ConclusionPre-DM is strongly and independently associated with stroke in Africans. Improving glycemic control through screening, healthy lifestyle and pharmacotherapy at a population level may be strategic in reducing the rising burden of stroke in Africa.

Teriparatide-associated calciphylaxis: a case series.

Calciphylaxis is a rare and potentially fatal small-vessel occlusive disease in which the tunica media becomes calcified, endothelial cells proliferate, and the tunica intima becomes thickened and fibrotic. Calciphylaxis typically occurs in the setting of end-stage renal disease with secondary hyperparathyroidism and elevated calcium-phosphorus product. The estimated incidence of calciphylaxis in dialysis or kidney transplant patients is 1 to 4%; however, the incidence of non-uremic calciphylaxis is unknown. We assessed postmarketing adverse event reports to further characterize cases of calciphylaxis associated with teriparatide. We searched for cases of teriparatide-associated calciphylaxis in the literature (EMBASE, PubMed) and those reported to FDA, including the FDA Adverse Event Reporting System, through March 31, 2021. We included calciphylaxis cases following teriparatide exposure of < 2years. Twelve cases described teriparatide-associated calciphylaxis. The median age was 81 (range 47-86) years. Eleven cases reported confirmatory biopsy and/or imaging. The median time-to-onset of calciphylaxis following teriparatide initiation was 3.5 (range 1-20) months. Three cases reported hospitalization, of which one resulted in death due to progression of the lesions. All cases had multiple risk factors (mean (SD), 4.5 (1.0)) including concomitant medications associated with calciphylaxis (12), female sex (11), and/or underlying autoimmune disease or other inflammatory disorder (10). We believe that exposure to teriparatide, coupled with underlying risk factors, may have triggered new-onset calciphylaxis. Expedited diagnosis and management by a clinician are important because calciphylaxis may be life-threatening and early intervention may improve outcomes.

Abstract P616: Characterization of the Associations Between Pre-Diabetes and Diabetes With Occurrence of Stroke by Its Types, Subtypes and Outcomes Among West Africans

Background: Pre-diabetes and diabetes mellitus (DM) are dysglycemic states associated with stroke occurrence. However, there is limited data from sub-Saharan Africa on the burden and associations between pre-DM and DM and stroke occurrence in a region experiencing an astronomic rise in stroke burden Purpose: To characterize the associations between stroke occurrence, types, subtypes, severity and outcome indicators according to glycemic status among West Africans. Methods: The Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with evidence of an acute stroke. Controls were age-and-gender matched stroke-free adults. Detailed evaluations for vascular, lifestyle, psychosocial factors, stroke severity and outcomes were performed. We used conditional logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval. Results: Among 2,935 stroke cases the mean age was 60.0 ± 14.2 years with 55.2% being males. By glycemic status, 931 (31.7%) were euglycemic, 633 (21.6%) had Pre-diabetes and 1371 (46.7%) had DM. The frequencies of euglycemia, pre-DM and DM among age- and sex-matched stroke-free controls were 69.2%, 13.3% and 17.5% respectively. Pre-diabetes was independently associated with stroke, adjusted odds ratio (95% CI) of 3.68 (2.61 - 5.21) as was having DM, aOR of 4.29 (3.19 - 5.74). The effect size of Pre-DM for ischemic stroke of 3.06 (95% CI: 2.01 - 4.64) was lower than that for DM of 4.82 (3.37-6.89). However, the effect size of Pre-DM for hemorrhagic stroke of 6.81 (95% CI: 3.29 - 14.08) is higher than 3.36 (1.94 - 5.86) for DM. Furthermore, the effect sizes of pre-DM for ischemic stroke subtypes were 9.64 (95% CI: 1.30-71.57) for cardio-embolic stroke, 3.64 (95% CI: 1.80-7.34) for small-vessel occlusive disease and 4.63 (95% CI: 0.80-26.65) for large-vessel disease. Conclusion: Every 2 out of 3 stroke cases admitted had a blood glucose abnormality. In addition to confirming the known associations between DM and stroke occurrence, we demonstrate that pre-DM is independently and more potently associated with hemorrhagic than ischemic strokes among West Africans.

HGPS (Hutchinson-Gilford -Progeria syndrome)

HGPS (Hutchinson-Gilford -Progeria syndrome) - JSAS- Print ISSN No: - Online ISSN No:- 2582-6387 Article DOI No:- 10.18231/j.jsas.2020.006, IP Journal of Surgery and Allied Sciences-IP J Surg Allied Sci

Influence of Sex Difference on Distribution of Risk Factors and Etiologic Subtypes of Acute Ischemic Stroke: Reality of Facts.

Sex-related differences have been documented in risk factors distribution, etiologic subtypes, diagnostic evaluation, offered management, and outcome of patients with acute ischemic stroke (AIS) from all over the world. Nevertheless, studies from Saudi Arabia are lacking. This study aimed to investigate the influence of sex on distribution of risk factors and etiologic subtype of AIS in patients admitted to our hospital. Record of patients admitted to King Fahd Hospital of the University between 2010 and 2017 with ischemic stroke (IS) were reviewed. Base line characteristics, risk factors, and etiologic subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification were compared between men and women. Among 453 patients with IS, 300 (66.2%) were men and 153 (33.7%) were women. The mean age of all patients was 61.5 ± 14.5 years. Women were older than men (P = 0.00). Hypertension (P = 0.00), atrial fibrillation (P = 0.00), and past history of stroke (P = 0.03) were more frequent in women compared to men. Fewer carotid Doppler studies (47.1 vs. 68.3%, P = 0.00) and echocardiogram (75.1 vs. 83%, P = 0.01) were done in women as compared to men. Cardioembolic etiologic subtype (26.1 vs. 17.7%) was found more frequently, whereas small vessel occlusive (23.5 vs. 31%) and large artery disease less (10.5 vs. 16.3%) frequently in women. Significant sex-related differences were found in risk factors and subtypes of AIS in our cohort of patients. Findings of our study are in general comparable with studies from all over the world.

Hyperhomocysteinemia can predict the severity of white matter hyperintensities in elderly lacunar infarction patients

Background and Purpose: Hyperhomocysteinemia (Hhcy) is a risk factor for stroke. Several studies have demonstrated that Hhcy was more closely linked to small vessel occlusive disease and white matter hyperintensities (WMH) in general and elderly population. Studies on WMH and homocysteine in elderly subjects are rare, and the results were inconsistent. Our study aimed to investigate the relationship between the serum homocysteine (HCY) and the severity of WMH in elderly lacunar stroke patients.Methods: Consecutive elderly (≥60 years old) lacunar infarction patients were recruited in this cross-sectional study. All patients were divided into two groups according to periventricular WMH (PVWMH) and deep WMH (DWMH) Fazekas scores. Patients with a Fazekas score (PVWMH or DWMH) of 0, 1, 2 were in mild-moderate group and 3 were in severe group. Vascular risk factors and clinical features were compared between these two groups. Multiple logistic regression analysis was used to determine the relationship between severity of WMH and vascular risk factors.Results: A total of 587 participants aged 60–95 years were enrolled. Patients with severe PVWMH (n = 178) had higher age (p = 0.030) and higher incidence of stroke history (p<0.001) than those in mild-moderate group. The level of serum HCY was significantly higher in patients with severe PVWMH (p ＝ 0.002). Patients with severe DWMH (n = 142) had higher age (p<0.001) and often had a history of stroke (p<0.001). The level of HCY was higher in patients with severe degree of DWMH, but had no significance (p ＝ 0.153). Multivariable logistic regression analyses showed Hhcy were independently associated with severe PVWMH after adjusted for age and vascular risk factors (p ＝ 0.014).Conclusions: Hhcy was independently associated with severe PVWMH of elderly lacunar stroke patients, but not DWMH.

Post-Sroke Mania: A Case Series in a Rural, Community Hospital

All patients had pre-existing moderate levels of small vessel occlusive disease and two had confirmed lacunar infarcts in the basal ganglia, while one had a small left sided fronto-parietal infarct consistent with the dysarthria-clumsy hand syndrome. Stroke was not initially recognized among these patients due to the absence of acute CT findings. Patients without pre-existing psychiatric diagnoses responded to low dose quetiapine. Two patients with pre-existing diagnoses of depression and anxiety, required higher doses.

An unusual case of paradoxical embolism in a young patient affected by stroke

The majority of ischemic strokes are due to atherothrombosis, cardioembolism, systemic hypoperfusion (general decrease in blood supply, e.g., in shock), or small vessel occlusive disease. However, many ischemic strokes occur without a well-defined etiology and are labeled as cryptogenic, and they constitute 30–40 % of all ischemic strokes. By the TOAST classification, which is the most commonly used in clinical practice, cryptogenic stroke (or stroke of undetermined origin in TOAST terminology) is defined as brain infarction that is not attributable to a source of definite cardioembolism, large artery atherosclerosis, or small artery disease despite extensive vascular, cardiac, and serologic evaluation. This means that in a large part of our patients we are unable to identify stroke etiology. In our report we described an unusual cause of stroke discovered by non-routinary investigations.

Racial-ethnic differences in stroke risk factors and subtypes: results of a prospective hospital-based registry

A majority of stroke research in the United States focuses on Caucasian and African-American populations, limiting the amount of comparative stroke data available on other racial and ethnic groups. The purpose of this research was to examine differences in stroke risk factors/subtypes between minority stroke patient groups in the United States (Asian-Indian, African-American, and Hispanic), using a Caucasian reference group. All patients had a comprehensive stroke work-up to ascertain their stroke risk factors and their stroke etiology applying TOAST criteria. Minority groups were younger compared with the white stroke patients, with the mean age significantly lower in the Asian-Indian and the Hispanic groups. The male:female ratio favored males in the Asian-Indian and Hispanic subgroups and females in the Caucasian and African-American groups. Diabetes was more prevalent in the minority subgroups, with a highest prevalence (55%) noted in the Asian-Indian group. The minority groups had lower prevalence of atrial fibrillation, carotid stenosis (≥70%), CAD, PVD, smoking, and alcohol use. The Asian-Indian stroke group had a higher median fasting plasma homocysteine level compared with the reference white group (12.1 vs. 10.4, p = 0.002). Compared to the reference white stroke group, the Asian-Indian stroke group had fewer strokes related to cardioembolism (7% vs. 25%) and a higher number of strokes related to small vessel occlusive disease (25% vs. 11%). There are some similarities in the stroke risk factors between the minority stroke groups, but the data indicate that there are different trends in stroke risk factors and subtypes.

What Is Certain When the Stroke Etiology Is Uncertain?

See related article, p 2948. > “Medicine is a science of uncertainty and an art of probability.” > > —William Osler (1849–1919) The great majority of ischemic strokes are due to cardioembolism, largeartery atherosclerotic disease, smallvessel occlusive disease, or other unusual mechanisms (eg, cervical dissection, thrombophilia, etc).1 Nevertheless, in approximately 20% to 40% of patients with stroke, the underlying etiology is not established (called “cryptogenic,” “uncertain,” or “undetermined” stroke).2,3 Limited information is available on longterm outcomes in this specific subgroup. Clinicians wonder about the risk of recurrence and whether death and/or disability in patients with cryptogenic stroke are better or worse compared with those with a determined etiology. In the present study, Nam et al studied 3278 patients with an ischemic stroke with a median followup of 3.4 years.4 Overall, 37% were classified as “undetermined.” Two thirds of patients had a mild stroke (National Institutes of Health Stroke Scale <6) with an overall median National Institutes of Health Stroke Scale of 4. Nearly 40% were exposed to smoking and 31% had diabetes. Interestingly, the authors broke down the undetermined strokes into …

Abstract 2661: Unique Attributes Of Asian-Indian Stroke/Transient Ischemic Attack (TIA) Patients: Results of a Prospective Multi-ethnic Hospital-based Registry

Introduction: The New Jersey Neuroscience Institute (NJNSI) serves the Middlesex County, NJ which, has a population of 750,000 (68.4% white, 7.3% Asian-Indian, 9.1% African-American, 15.2% others; 13.6% Hispanic of any race, based on 2000 US Census). This prospective multi-ethnic hospital-based registry provides a unique opportunity to study Asian-Indian stroke/TIA patients. Hypothesis: There are differences of stroke risk factors/subtypes between Asian-Indian and Caucasian stroke/TIA patient groups, in light of similar differences noted in the African-American and Hispanic groups individually in relation to the Caucasian group. Methods: Between 1998 and 2009, data on stroke risk factors and stroke subtypes were collected on 1100 consecutive stroke/TIA patients (1037 or 94.3% non-Hispanic; 63 or 5.7% Hispanic) admitted to the NJNSI. Of the non-Hispanics, 768 (74.1%) were Caucasian, 99 (9.6%) Asian-Indian, 139 (13.4%) African-American, 31 (3.0%) were others. Stroke risk factors assessed included age, gender, hypertension, diabetes, atrial fibrillation evaluated by 48-hour Holter monitor, hyperlipidemia evaluated by fasting lipid profile, prevalent coronary artery disease, smoking history, alcohol use, carotid stenosis (&gt;70%) evaluated by duplex ultrasound, fasting homocysteine level and stroke subtypes (using TOAST classification). Asian-Indians, African-American and Hispanic groups were individually compared with the Caucasian group (control) in this study using odds ratio (OR) analyses and X2 test for categorical variables and t-test for continuous variables. Results: The Asian-Indian group was younger (66±12 vs 72±14, p &lt;0.001), higher proportion of males (OR 2.1, p=0.001) and diabetes (OR 2.3, p&lt; 0.001); lower proportion of atrial fibrillation (OR 0.2, p&lt;0.001), smokers (OR 0.3, p&lt;0.001), Alcohol users (OR 0.4, p=0.003) and higher fasting plasma homocysteine level (17.2±20.3 vs 11.9±7.4, p=0.002). There were fewer strokes related to cardioembolism (OR 0.2, p&lt;0.0001) and a higher number of strokes related to small vessel occlusive disease (OR 2.4, p = 0.001). The African-American group had lower proportion of carotid stenosis (OR 0.5, p=0.007) and atrial fibrillation (OR 0.6, p=0.034). African-American group had higher levels of fasting triglyceride level (Median 92 vs 122 mg/dL). The Hispanic group resembled the Asian-Indian group in that they were younger (64±16 vs 72±14, p&lt; 0.001), had a higher proportion of diabetes (OR 1.7, p=0.039), lower proportion of atrial fibrillation (OR 0.5, p=0.037) than the Caucasian group. Conclusions: The Asian-Indian stroke/TIA group in this community has unique attributes in respect to stroke risk factors and stroke subtype. There are few similarities in the stroke risk factors with the Hispanic stroke/TIA group.

Treatment of acute ischemic stroke: beyond thrombolysis and supportive care.

The initial therapeutic approach to acute ischemic stroke consists of thrombolytic therapy and early initiation of supportive care, usually commenced prior to the determination of the underlying stroke etiology. Varying stroke mechanisms may call for specific, etiology-based treatment. The majority of strokes result from cardioembolism, large-vessel atherothromboembolism, and small-vessel occlusive disease. There are scant data to support the use of acute anticoagulation therapy over anti-platelet therapy in cardioembolic stroke and large-vessel atherosclerosis, although it may be reasonable in a certain subset of patients. However, augmentation of blood flow with early surgery, stenting, or induced hypertension, may play a role in patients with large artery stenosis. The less commonly identified stroke mechanisms may warrant special consideration in treatment. Controversy remains regarding the optimal anti-thrombotic treatment of arterial dissection. Reversible cerebral vasoconstriction syndrome may benefit from therapy with calcium channel blockers, high-dose steroids, or magnesium, although spontaneous recovery may occur. Inflammatory vasculopathies, such as isolated angiitis of the central nervous system and temporal arteritis, require prompt diagnosis as the mainstay of therapy is immunosuppression. Cerebral venous thrombosis is a rare cause of stroke, but one that needs early identification and treatment with anticoagulation. Rapid determination of stroke mechanism is essential for making these critical early treatment decisions.

Myeloproliferative Disorder as the Cause of Peripheral Ischemia in a Young Patient

A 35-year-old patient with rest pain and peripheral gangrene was referred with a diagnosis of Takayasu's disease but had myeloproliferative disorder (primary thrombocythemia). The angiogram revealed surgically noncorrectable small vessel occlusive disease with no evidence of atheroma. Medical therapy with cytotoxic and antiplatelet agents achieved satisfactory results with excellent wound healing after surgical amputation of necrotic tissue. The need for early diagnosis of this condition is emphasized.

Manifestaciones neurológicas de la enfermedad de Fabry

To present a review of the neurological manifestations, diagnosis and treatment of Fabry disease. Fabry disease is a hereditary deficiency of lisosomal alpha-galactosidase A resulting in accumulation of globotriaosylceramide in vascular endothelium and smooth-muscle cells. Neurological manifestations include severe attacks of neuropathic pain and acroparesthesias at early age and small-vessel occlusive disease in adults. Other manifestations are renal dysfunction, cardiomyopathy, abdominal pain, deafness, angiokeratoma and corneal opacity. Cerebrovascular involvement results from small-arteries lipid deposition, impairment in cerebrovascular reactivity, vertebrobasilar ectasia as well as vascular risk factors such as nephrogenic hypertension and cardiac disease. Fabry disease prevalence seems to be higher than previously described and currently many patients might be underdiagnosed. Fabry disease must be included in the differential diagnosis of stroke in young people, particularly in those with criptogenic etiology, vertebrobasilar location and renal dysfunction. The diagnosis has important therapeutic implications since it is available a replacement therapy with agalsidase, a recombinant enzyme which has been effective in lipid tissue clearance and clinical improvement in Fabry patients.

INVITED COMMENTARY

Coronary artery bypass grafting (CABG) with saphenous vein conduits is one of the most commonly performed surgical procedures worldwide. Unfortunately, saphenous vein graft patency is only 50% at 10 years. As a result, there has been a growing interest in the use of arterial conduits, particularly the radial artery (RA), as excellent midterm patency results of more than 90% have been reported. Nevertheless, concerns have been raised about decreased blood flow to the hand with potential morbidity after RA harvesting. This paper by Knobloch and colleagues describes a novel combined laser-Doppler flowmeter system that can be used to measure palmar microcirculation in attempts to avoid ischemic complications of the hand. Palmar circulation was evaluated using the laser-Doppler flowmeter before and 2 days after RA harvesting. Patients were tested for either complete suprasystolic occlusion of the brachial artery or alternate occlusion of the radial and ulnar arteries. As expected, changes in both blood flow and tissue oxygenation saturation decreased with various occlusive maneuvers. After RA harvest, tissue flows and saturations were the same as for the nondonor hand. This “proof-of-concept” study is small with only 15 patients, all of whom were less than 60 years of age. One wonders how well this system would work in the elderly, smoking, or diabetic population with small vessel occlusive disease. By including more patients and then applying a subgroup analysis, the authors might have answered this question. The Allen test is simple and safe, and is performed commonly to assess palmar circulation. Unfortunately, the authors make no mention of whether concomitant Allen testing was performed in any of these patients. Furthermore, there are no comparative results or descriptions of how the device might be more reliable than the Allen test. Correlation with the laser-Doppler flowmeter system would have been interesting and would have validated the utility. Nevertheless, one of the more interesting points of the paper was that despite reduction in palmar blood flow and tissue oxygen saturation with RA harvesting, 2 days postoperatively both tissue oxygen saturation and blood flow were not reduced compared with the other hand and, more importantly, compared with preoperative values. Potential mechanisms might include increased compensatory blood flow from the remaining artery or the opening of small collaterals within the palmar arch hand. This finding raises a critical point in the use of this new technology. Should decreases in blood flow and tissue oxygen saturation be disregarded as they return to baseline 2 days after RA harvest, or is there some dangerous threshold before RA harvesting that can be detected by this new method? In summary, further work will need to include a wider patient population to determine whether this technology can add more clinical information for patients whose RA is harvested. Moreover, will this device predict and detect who may have postoperative ischemic complications? This important question must be answered before surgeons can conclude that the laser-Doppler flowmeter will add functional information that goes beyond the Allen test.

Gene Therapy for the Extension of Vein Graft Patency: A Review

The mainstay of treatment for long-segment small-vessel chronic occlusive disease not amenable to endovascular intervention remains surgical bypass grafting using autologous vein. The procedure is largely successful and the immediate operative results almost always favorable. However, the lifespan of a given vein graft is highly variable, and less than 50% will remain primarily patent after 5 years. The slow process of graft malfunction is a result of the vein's chronic maladaptive response to the systemic arterial environment, its primary component being the uncontrolled proliferation of vascular smooth muscle cells (SMCs). It has recently been suggested that this response might be attenuated through pre-implantation genetic modification of the vein, so-called gene therapy for the extension of vein graft patency. Gene therapy seems particularly well suited for the prevention or postponement of vein graft failure since: (1) the stimulation of SMC proliferation appears to largely be an early and transient process, matching the kinetics of current gene transfer technology; (2) most veins are relatively normal and free of disease at the time of bypass allowing for effective gene transfer using a variety of systems; and (3) the target tissue is directly accessible during operation because manipulation and irrigation of the vein is part of the normal workflow of the surgical procedure. This review briefly summarizes the current knowledge of the incidence and basic mechanisms of vein graft failure, the vector systems and molecular targets that have been proposed as possible pre-treatments, the results of experimental genetic modification of vein grafts, and the few available clinical studies of gene therapy for vascular proliferative disorders.

Clinical Course and Surgical Management of Massive Cerebral Infarction

Acute occlusion of the proximal middle cerebral artery (MCA) can lead to rapid development of fatal brain swelling and ischemic strokes. Decompressive surgery, if performed early in this subpopulation of patients, can reduce mortality and result in a favorable outcome. In this article, we describe our surgical approach for treating malignant MCA syndrome and compare it with other management strategies. This is a retrospective review of patients who developed acute occlusion of the proximal MCA and underwent aggressive surgical decompression (large craniectomy, anterior temporal lobectomy, resection of infarcted tissue, and duraplasty). The outcome of this management strategy is compared with the previously published outcomes of hemicraniectomy and dural augmentation. Twelve patients were included in the study. The group consisted of six men and six women (mean age, 46.8 yr). Nine patients had right MCA stroke, and three had left MCA infarction. The causes of the strokes were cardioembolic, iatrogenic, small-vessel occlusive disease, and others. The interval between infarction and clinical evidence of herniation varied from 24 hours to 10 days. Two patients died, five were independent or had moderate disabilities, and five had severe disability. Surgical decompression consisting of a large craniectomy, anterior temporal lobectomy, resection of infarcted tissue, and duraplasty is beneficial to a significant number of patients with massive MCA stroke and clinical signs of herniation.

Natural History of Intra-cardiac Thrombus in Stroke/TIA Patients

P209 Background Intra-cardiac thrombus is a potential source of embolus leading to ischemic cerebrovascular event. The natural history of intra-cardiac thrombus is not known. Objectives To examine the natural history of intra-cardiac thrombus detected by TEE in stroke/TIA patients. Methods Eighty-one patients with recent stroke/TIA underwent sequential TEE evaluations at ≤7 days and 9 months from the symptom onset to detect intra-cardiac thrombus (mean age 60, 39 males and 60 black). The TEEs were recorded on VHS videotape and systematically evaluated by two blinded cardiologists for evidence and location of intra-cardiac thrombus (λ=0.72). In case of a disagreement it was adjudicated by a third blinded cardiologist. The stroke risk factors and stroke preventive medications were recorded in patients with and without intracardiac thrombus and compared using χ 2 test. Results An intra-cardiac thrombus was found in the initial TEE in 18 (22%) patients (2 in left atrium, 13 in left atrial appendage, 3 in left ventricle) and in the follow-up 9 month TEE in 9 (11%) patients (8 in left atrial appendage, 1 in left ventricle). The intracardiac thrombus had disappeared in 14 (78%) patients in a period of 9 months (2 in left atrium, 9 in left atrial appendage and 3 in left ventricle). Disappearance of intracardiac thrombus correlated strongly with patients anticoagulated with Warfarin (p&lt;0.0001). A new intracardiac thrombus was detected only on the 9 month TEE in 5 (6%) patients (5 in the left atrial appendage, none in the left atrium or left ventricle). The patients with new intracardiac thrombus were significantly (p=0.02) older (mean±SD=70±7 yrs) as compared to those without (59±12 yrs). Three out of five patients with new cardiac thrombus were felt to have small vessel occlusive disease and were on antiplatelet therapy. Conclusions Anticoagulation with warfarin for 9 months can result in disappearance of intracardiac thrombus in stroke/TIA patients. Anticoagulation with Warfarin may have a therapeutic role in stroke/TIA patients with intracardiac thrombus. Older patients with lacunar strokes and not on anticoagulation are prone to develop an new intracardiac thrombus.

Angiotropic Large-Cell Lymphoma Presenting as Pulmonary Small Vessel Occlusive Disease

Angiotropic lymphoma (AL) is an unusual variant of extranodal lymphoma, characterized by massive proliferation of neoplastic lymphoid cells almost exclusively within blood vessels. Whereas the lymphoid origin of this disease is widely accepted it still remains unclear whether AL is a distinct entity that originates in the blood vessels or whether it represents a form of secondary intravascular dissemination of a primary solid lymphoma. The present case is unusual because death by right heart failure owing to extensive intravascular proliferation of neoplastic cells and subsequent occlusion of pulmonary blood vessels has not been described so far. In addition, the patient had suffered from a solid deposit of a large-cell B-lymphoma months before the angiotropic manifestation, suggesting that AL might develop out of more common types of non-Hodgkin's lymphomas.