Presence Of Small Vessel Disease Research Articles

Subpleural Perfusion as a Predictor for a Poor Surgical Outcome in Chronic Thromboembolic Pulmonary Hypertension

Small vessel disease is a major determinant of poor outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension (CTEPH). Out-of-proportion pulmonary vascular resistance (PVR) may indicate the presence of small vessel disease, but it is a very subjective evaluation. We investigated poor subpleural perfusion as a marker for small vessel disease and assessed its association with disease severity and surgical outcome of CTEPH. We assessed the subpleural perfused area in the capillary phase of pulmonary angiography in 104 consecutive patients, including 45 who underwent surgery, and then divided the patients into either the well-perfused group (the subpleural space in at least one segment was well perfused [n = 75]) or the poorly perfused group (subpleural spaces were either unperfused or minimally perfused in all segments [n = 29]). We compared the pulmonary hemodynamics, degree of distal thrombi, and surgical outcome between these two groups. The poorly perfused group had significantly higher PVR (937 ± 350 dyne/s/cm(5) vs 754 ± 373 dyne/s/cm(5), P = .02) and more distal thrombi, resulting in fewer surgically treated patients (27.6% vs 49.3%, P = .04) compared with the well-perfused group. This group showed a higher surgical mortality (62.5% vs 2.7%) and higher postoperative PVR (656 ± 668 dyne/s/cm(5) vs 319 ± 223 dyne/s/cm(5), P = .04). Even in a multivariate analysis, poor subpleural perfusion was associated with surgical mortality. Poor subpleural perfusion in the capillary phase of pulmonary angiography might be related to small vessel disease and a poor surgical outcome of CTEPH.

Mild Cognitive Impairment: Beyond Memory Dysfunction

Traditionally, mild cognitive impairment (MCI) has tended to be primarily characterised and diagnosed in relation to the integrity of amnestic function and thus studied accordingly. However, a more recent multidisciplinary and collaborative research approach has investigated a much wider range of cognitive, functional, structural, and behavioural integrity and is revealing an extensive and often complex range of characteristics in addition to memory dysfunction that differentiate MCI from healthy ageing. These may be of especial relevance when considering MCI as a potential prodromal stage of dementia. Several papers in this special issue report novel and important findings with respect to the search for predictors of development of dementia in patients with MCI. The paper by E. L. Abner et al. describes a new approach in the assessment of risk factors for dementia, including age, gender, education, apolipoprotein E status, family history of dementing illness, and baseline hypertension. Their results highlight the importance of objective criteria in MCI diagnosis. I. Reinvang et al. report on how studies of genetic high-risk groups, using sensitive cognitive neuroscience paradigms, indicate the potential for differences in executive function to be a cognitive marker useful for tracking development of the pathophysiological changes of Alzheimer’s disease (AD). The paper by D. V. Moretti et al. reveals specific electroencephalographic (EEG) changes associated with atrophy of the hippocampus in people with MCI and AD, namely, that the increase of alpha3/alpha2 power ratio is correlated with atrophy of the hippocampus both in MCI and in AD patients, suggesting a possible diagnostic role of EEG markers. In a comprehensive review, B. Ferencz et al. provide an overview of brain changes in early AD and MCI, together with evidence for recent advances in neuroimaging and genetic biomarkers and the importance of altered mitochondrial dynamics in the preclinical stages of AD. D. P. Devanand et al. discuss the outcome of their detailed and novel study that uses clinical and magnetic resonance imaging (MRI) variables to compare predictor models for the transition to AD in patients with MCI. Research priority has until relatively recently been directed to the amnestic type of mild cognitive impairment (aMCI). However, the paper by A. Poggesi et al. provides an important overview of the concept of vascular MCI and how it may signal the prodromal stages of vascular dementia or the presence of small vessel disease. It is of course important to raise awareness of MCI within the public at large and also to determine the factors likely to encourage individuals to report a change in their memory to their general practitioner. C. Pires et al. highlight the importance of the type of memory complaint in determining whether an individual seeks medical attention and describe how forgetting the name of family members or friends is a particularly strong impetus for such contact. Increasingly, studies are addressing the potential of MCI to adversely affect a wide range of factors that impinge upon an individual’s quality of life. In the paper by G. Arsenault-Lapierre et al., the importance of stress in the lives of those with MCI and dementia is described, together with the finding that patients with MCI or dementia can display anosognosia, which can preclude patients from accurately appraising their own level of stress. Together these papers contribute to our further understanding of the concept of MCI and of its potential progression to dementia. All highlight the need to think beyond merely memory dysfunction in MCI and to continue to expand our knowledge in this important field of scientific and clinical research.

Association of Central Systolic Blood Pressure With Intracerebral Small Vessel Disease in Japanese

Recent studies have reported the association between advanced arterial stiffness and brain small vessel diseases (SVDs). Two possible hemodynamic mechanisms, increases in central blood pressure (BP) and pulsatile flow load to the brain, have been speculated to link arterial stiffness and SVD. The carotid flow augmentation index (AI) has been proposed as an index of pulsatile flow to the brain. We compared its association with brain SVD with that of central BP in a general population. Subjects were 500 individuals free from symptomatic cardiovascular diseases with a mean age of 66.9 +/- 8.4 years. Brachial-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. Carotid flow AI was obtained by Doppler ultrasonography. The presence of silent cerebral lacunar infarcts (SCI) was determined as a manifestation of SVD by 3-tesla magnetic resonance imaging (MRI). Second peak radial systolic BP (SBP2) and pulse pressure (PP2) were used as estimates of central BP. baPWV was significantly associated with radial BP2 (r = 0.55, P < 0.0001) but not with carotid flow AI (r = 0.03, P = 0.51). Radial BPs and baPWV, but not flow AI, were significantly higher in subjects with SCI. Radial SBP2 had higher odds ratio for the presence of SCI than brachial SBP, PP, and radial PP2. Logistic regression analysis showed that radial SBP2, but not flow AI, was independently related to the presence of SCI. These findings indicate that the SBP2, an estimate of central SBP, is significantly associated with the presence of SVD in an apparently healthy general population.

Cerebral Microvascular Disease Predicts Renal Failure in Type 2 Diabetes

Abnormalities in small renal vessels may increase the risk of developing impaired renal function, but methods to assess these vessels are extremely limited. We hypothesized that the presence of small vessel disease in the brain, which manifests as silent cerebral infarction (SCI), may predict the progression of kidney disease in patients with type 2 diabetes. We recruited 608 patients with type 2 diabetes without apparent cerebrovascular or cardiovascular disease or overt nephropathy and followed them for a mean of 7.5 years. At baseline, 177 of 608 patients had SCI, diagnosed by cerebral magnetic resonance imaging. The risk for the primary outcome of ESRD or death was significantly higher for patients with SCI than for patients without SCI [hazard ratio, 2.44; 95% confidence interval (CI) 1.36 to 4.38]. The risk for the secondary renal end point of any dialysis or doubling of the serum creatinine concentration was also significantly higher for patients with SCI (hazard ratio, 4.79; 95% CI 2.72 to 8.46). The estimated GFR declined more in patients with SCI than in those without SCI; however, the presence of SCI did not increase the risk for progression of albuminuria. In conclusion, independent of microalbuminuria, cerebral microvascular disease predicted renal morbidity among patients with type 2 diabetes.

Living Beyond Our Physiological Means

It is our premise that the pathophysiology of small vessel disease in the brain is similar to small vessel disease in other heavily perfused tissues and that the presence of small vessel disease elsewhere in the body foretells its presence in the brain as well as its consequences on cognitive function. The hypothesis presented in this article is that small vessel disease is a systemic condition of aging that is exacerbated by vascular risk factors, which results from dysfunction of arteriolar perfusion. This condition, which we term systemic arteriolar dysfunction, affects the brain as well as a number of extracranial systems. Recent literature is synthesized to suggest a possible etiology of this condition, highlighting the multiple pathways that may conspire to produce the endothelial and other vascular changes seen in systemic arteriolar dysfunction. Regardless of the etiology, we emphasize that small vessel disease is a systemic condition with major healthcare consequences, requiring a new paradigm in the way we practice medicine. Because this condition can be decelerated by control of vascular risk factors, doing so may significantly reduce morbidity, mortality, and healthcare costs.

Cerebral Small Vessel Disease-Induced Apolipoprotein E Leakage Is Associated With Alzheimer Disease and the Accumulation of Amyloid β-Protein in Perivascular Astrocytes

Apolipoprotein E (apoE) plays a role in the pathogenesis of Alzheimer disease (AD). It is involved in the receptor-mediated cellular clearance of the amyloid beta-protein (Abeta) and in the perivascular drainage of the extracellular fluid. Microvascular changes are also associated with AD and have been discussed as a possible reason for altered perivascular drainage. To further clarify the role of apoE in the perivascular and vascular pathology in AD patients, we studied its occurrence and distribution in the perivascular space, the perivascular neuropil, and in the vessel wall of AD and control cases with and without small vessel disease (SVD). Apolipoprotein E was found in the perivascular space and in the neuropil around arteries of the basal ganglia from control and AD cases disclosing no major differences. Western blot analysis of basal ganglia tissue also revealed no significant differences pertaining to the amount of full-length and C-terminal truncated apoE in AD cases compared with controls. In contrast, Abeta occurred in apoE-positive perivascular astrocytes in AD cases but not in controls. In blood vessels, apoE and immunoglobulin G were detected within the SVD-altered vessel wall. The severity of SVD was associated with the occurrence of apoE in the vessel wall and with that of Abeta in perivascular astrocytes. These results point to an important role of apoE in the perivascular clearance of Abeta in the human brain. The occurrence of apoE and immunoglobulin G in SVD lesions and in the perivascular space suggests that the presence of SVD results in plasma-protein leakage into the brain. It is therefore tempting to speculate that apoE represents a pathogenetic link between SVD and AD.

Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke

To evaluate whether the presence of leukoaraiosis or multiple lacunes is associated with symptomatic intracerebral hemorrhage (ICH) and 90-day outcome after thrombolytic treatment with tissue plasminogen activator (tPA). Data were from a Canadian national registry of thrombolyzed patients with ischemic stroke. A total of 820 scans were assessed, blind to clinical features, for the presence of severe vs no/moderate leukoaraiosis, and of multiple (>2) vs no/single lacunar infarcts. Logistic regression was used to determine if an independent interaction existed between the presence and degree of leukoaraiosis/lacunes and risk of symptomatic ICH, and to evaluate the predictive role of leukoaraiosis and lacunes in relation to 90-day outcome. An overall symptomatic ICH rate of 3.5% was observed. The rate of symptomatic ICH increased up to 10% in patients with severe leukoaraiosis and multiple lacunes. A significant association was observed between ICH risk and either severe leukoaraiosis (RR = 2.7 [95% CI 1.1 to 6.5]) or multiple lacunes (RR = 3.4 [95% CI 1.5 to 7.6]). Patients with multiple lacunes, but not leukoaraiosis, had higher mortality at 90 days compared to those with one or no lacunes (OR = 2.9, 95% CI 1.3 to 6.2, p = 0.008). No difference was observed in the good outcome rate among patients with and without leukoaraiosis or lacunes or both. The presence of small vessel disease on CT scan does not affect overall clinical outcome at 3 months in routine community use of tPA for ischemic stroke. A significant increase in the risk of symptomatic ICH is observed.

Island toe flaps in neurotrophic ulcers of the foot and ankle.

Eight plantar island toe flaps for the management of 7 neurotrophic ulcers of the foot and ankle are presented. The plantar vascular anatomy is reviewed with emphasis on functional features and alternate sources of supply. The surgical technique closely parallels that of the Littler neurovascular island flap in the hand. The release of the plantar fascia by incision is the most important technical step in the flap transfer. The procedure is advantageous because it substitutes weight-bearing skin, causes minimal disruption of the plantar anatomy, and is effective even in the presence of small vessel disease.

Myocardial blood flow in coronary artery disease: Studies at rest and during stress with inert gas washout techniques

HIS article will review techniques using inert gases that have been utilized to measure average left ventricular and regional myocardial blood flow in man. The development of these techniques has been spurred primarily by the desire to evaluate clinically the disturbances of myocardial blood flow that occur in patients with coronary artery disease. Coronary atherosclerosis is a focal process that affects primarily large epicardial coronary arteries and their major branches and to a lesser extent the smaller intramyocardial vessels.‘,’ Discrete coronary lesions produce alterations in myocardial blood flow both in different regions of the heart (i.e., spatial heterogeneity of blood flow) and also in different layers of the ventricular wall (i.e., transmural heterogeneity of blood flow). In turn, these blood flow alterations in the myocardium may impair cardiac performance. Both global and segmental abnormalities of ventricular contraction are associated with coronary artery disease.” When the blood flow to a region of the myocardium is insufficient to meet the metabolic requirements of the working heart muscle for oxygen, &hernia develops and may produce angina pectoris, myocardial infarction, and/or local abnormalities of cardiac metabolism and function. Coronary arteriography is commonly used to visualize the extent and distribution of coronary artery obstructions. It is a necessary prerequisite to consideration of surgical therapy for angina, infarction, or ventricular failure.+ However, coronary arteriography does not reveal to what degree myocardial blood flow has been compromised by the obstructing lesion. It cannot reveal the presence of small vessel disease (i.e., abnormal vessels < 200~ in diameter) nor the extent