Vessel Wall Imaging of Intracranial Arteries: Fundamentals and Clinical Applications.

With the increasing use of 3-tesla MRI scanners and the development of applicable sequences, it has become possible to achieve high-resolution, good contrast imaging, which has enabled the imaging of the walls of small-diameter intracranial arteries. In recent years, the usefulness of vessel wall imaging has been reported for numerous intracranial arterial diseases, such as for the detection of vulnerable plaque in atherosclerosis, diagnosis of cerebral arterial dissection, prediction of the rupture of cerebral aneurysms, and status of moyamoya disease and cerebral vasculitis. In this review, we introduce the histological characteristics of the intracranial artery, discuss intracranial vessel wall imaging methods, and review the findings of vessel wall imaging for various major intracranial arterial diseases.

Dolichoectasia: a brain arterial disease with an elusive treatment.

INTRODUCTION: Dolichoectasia is a form of brain large artery disease associated with a high risk of mortality and morbidity. Progressive enlargement of arterial size is a predictor of mortality, but there are no specific treatments for arresting or slowing down dilatation. Additionally, dilated brain arteries can cause flow stagnation, which can trigger thrombosis and cause stroke. Pathology and genetic studies indicate a possible role for increased matrix metalloproteinase activation in arterial dilatation and thus in the pathophysiology of dolichoectasia. Therefore, therapeutic interventions aimed at slowing down arterial dilatation and preventing thrombosis could hypothetically play a role in treating patients with dolichoectasia. METHODS: We present four patients with dolichoectasia that exemplify therapeutic challenges worth discussing in the context of the current literature. Two patients were treated off-label with doxycycline (based on its antiMMP properties) and with apixaban, one patient was put on warfarin and later switched to aspirin, and the fourth patient underwent endovascular treatment. RESULTS: We report four cases, all men 50 years or older. Of the two patients treated with doxycycline, we noted a slowdown of the basilar artery (BA) growth, but the BA continued to grow in the other patient. Of the two patients who received apixaban, none had a subsequent stroke in 5 and 4 years of follow-up, respectively. One patient was admitted with a fatal BA thrombosis and rupture, and pathological examination of the brain arteries demonstrated advanced arterial wall degeneration but no atherosclerosis. DISCUSSION: These cases exemplify the challenges of treating people with dolichoectasia and highlight the need for better evidence regarding the best possible treatment for this population.

A cross-sectional, case-control study of intracranial arterial wall thickness and complete blood count measures in sickle cell disease.

In sickle cell disease (SCD), cerebral oxygen delivery is dependent on the cerebral vasculature's ability to increase blood flow and volume through relaxation of the smooth muscle that lines intracranial arteries. We hypothesised that anaemia extent and/or circulating markers of inflammation lead to concentric macrovascular arterial wall thickening, visible on intracranial vessel wall magnetic resonance imaging (VW-MRI). Adult and pediatric SCD (n = 69; age = 19.9 ± 8.6 years) participants and age- and sex-matched control participants (n = 38; age = 22.2 ± 8.9 years) underwent 3-Tesla VW-MRI; two raters measured basilar and bilateral supraclinoid internal carotid artery (ICA) wall thickness independently. Mean wall thickness was compared with demographic, cerebrovascular and haematological variables. Mean vessel wall thickness was elevated (P < 0·001) in SCD (1·07 ± 0·19 mm) compared to controls (0·97 ± 0·07 mm) after controlling for age and sex. Vessel wall thickness was higher in participants on chronic transfusions (P = 0·013). No significant relationship between vessel wall thickness and flow velocity, haematocrit, white blood cell count or platelet count was observed; however, trends (P < 0·10) for wall thickness increasing with decreasing haematocrit and increasing white blood cell count were noted. Findings are discussed in the context of how anaemia and circulating inflammatory markers may impact arterial wall morphology.

Intracranial Arterial Calcification: Prevalence, Risk Factors, and Consequences: JACC Review Topic of the Week.

Intracranial large and small arterial calcifications are a common incidental finding on computed tomography imaging in the general population. Here we provide an overview of the published reports on prevalence of intracranial arterial calcifications on computed tomography imaging and histopathology in relation to risk factors and clinical outcomes. We performed a systematic search in Medline, with a search filter using synonyms for computed tomography scanning, (histo)pathology, different intracranial arterial beds, and calcification. We found that intracranial calcifications are a frequent finding in all arterial beds with the highest prevalence in the intracranial internal carotid artery. In general, prevalence increases with age. Longitudinal studies on calcification progression and intervention studies are warranted to investigate the possible causal role of calcification on clinical outcomes. This might open up new therapeutic directions in stroke and dementia prevention and the maintenance of the healthy brain.

Comprehensive investigation of RNF213 nonsynonymous variants associated with intracranial artery stenosis.

Intracranial artery stenosis (ICAS) is the most common cause of ischemic stroke worldwide. RNF213 single nucleotide variant c.14429G > A (p.Arg4810Lys, rs112735431) was recently reported to be associated with ICAS in East Asians. However, the disease susceptibility of other RNF213 variants has not been clarified. This study comprehensively investigated ICAS-associated RNF213 variants in a pool of 168 Japanese ICAS patients and 1,194 control subjects. We found 138 nonsynonymous germline variants by target resequencing of all coding exons in RNF213. Association study between ICAS patients and control subjects revealed that only p.Arg4810Lys had significant association with ICAS (P = 1.5 × 10-28, odds ratio = 29.3, 95% confidence interval 15.31-56.2 [dominant model]). Fourteen of 138 variants were rare variants detected in ICAS patients not harboring p.Arg4810Lys variant. Two of these rare variants (p.Cys118Arg and p.Leu2356Phe) consistent with variants previously reported in moyamoya disease patients characterized by stenosis of intracranial artery and association with RNF213, and three rare variants (p.Ser193Gly, p.Val1817Leu, and p.Asp3329Tyr) were found neither in control subjects and Single Nucleotide Polymorphism Database. The present findings may improve our understanding of the genetic background of intracranial artery stenosis.

Small dense low-density lipoprotein cholesterol is strongly associated with NIHSS score and intracranial arterial calcification in acute ischemic stroke subjects.

Intracranial artery calcification (IAC) is an important risk factor for cerebral infarction and a key biomarker for intracranial artery stenosis. Small dense low-density lipoprotein cholesterol (sd-LDL-c) was independently associated with increased cardiovascular events and coronary calcification. Our study assessed whether sd-LDL-c is an independent factor for IAC in acute ischemic stroke (AIS) patients. This cross-sectional study involved a total of 754 patients with AIS (mean age: 65 ± 13.2 years). All the patients had received brain computed tomography angiography (CTA) examination to evaluate IAC. Serum sd-LDL-c levels and other biochemical parameters were analyzed. Admission NIHSS score and mRS score at discharge were collected. After 60-days 85 patients died during hospitalization and follow-up. Partial correlation analysis showed that serum sd-LDL-c levels were associated with admission NIHSS score and IAC score after adjusted age and gender. Logistic regression analysis showed that serum sd-LDL-c levels independently predicted NIHSS scores (ß = 1.537, 95%CI: 0.134-2.878, p = 0.042) and IAC scores (ß = 1.355, 95%CI: 0.319-2.446, p = 0.015). The average level of sd-LDL-c in patients who died was also significantly increased compared to survival patients (1.04 ± 0.59 vs 0.88 ± 0.44 mmol/L, p = 0.017). However, multivariate logistic regression analysis showed serum sd-LDL-c levels could not predict all-cause mortality and prognosis in AIS patients. Our study found that sd-LDL-c as a strong atherogenic lipid particle can independently predict admission NIHSS scores and the severity of cerebral artery calcification in AIS patients. However, its prognostic value in AIS patients still needs further study in the future.

Basi-parallel anatomic scanning (BPAS-MRI) compared with high-resolution MRI for the diagnosis of vertebrobasilar artery abnormalities.

PURPOSE: To investigate the utility of basi-parallel anatomic scanning magnetic resonance imaging (BPAS-MRI) for the diagnosis of vertebrobasilar artery lesions. METHOD: From October 2017-November 2018, 105 consecutive patients with abnormal configuration of the vertebrobasilar artery on time-of-flight magnetic resonance angiography (TOF-MRA) were enrolled. Conventional high-resolution MRI combined with TOF-MRA were performed to diagnose lesions and were used as the standard for sensitivity and specificity determination. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BPAS-MRI combined with TOF-MRA were calculated. The consistencies between the two methods were evaluated by kappa test. RESULTS: Of the 105 patients, 45 were diagnosed with arteriosclerosis, 46 with vertebral artery dysplasia, 11 with artery dissection or dissecting aneurysm, and 3 as simple dilatation. Results Compared with conventional high-resolution MRI combined with TOF-MRA, for vertebrobasilar arteriosclerosis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BPAS-MRI combined with TOF-MRA were 95.6 %, 95.0 %, 93.5 %, 96.6 % and 95.2 %, respectively and kappa value was 0.903. For vertebral artery dysplasia, they were 100 %, 96.6 %, 95.8 %, 100 %, and 98.1 %, respectively and kappa value was 0.961. For vertebrobasilar artery dissection or dissection aneurysm, they were 81.8 %, 96.8 %, 97.8 %, 75.0 % and 95.2 %, respectively and kappa value was 0.756. CONCLUSIONS: BPAS-MRI can show the outer contour of the vertebrobasilar artery system. Combined with TOF-MRA, it may be used to differentiate among vertebrobasilar artery abnormalities, and be used in hospitals where conventional high-resolution MRI is not feasible.

Vascular Cognitive Disorder.

The term vascular cognitive disorder (VCD) refers to a heterogeneous group of disorders in which the primary feature is cognitive impairment attributable to cerebrovascular disease (CVD). This includes not only vascular dementia (VaD) but also cognitive impairment of insufficient severity to meet diagnostic criteria for dementia. VCD is recognized as the second most common cause of dementia after Alzheimer's disease (AD), but prevalence rates vary widely according to the diagnostic criteria employed. There have been recent attempts to standardize diagnostic criteria. VCD incorporates a range of neuropathological mechanisms including poststroke impairment, small and large vessel disease, and cases of mixed-pathology, with CVD interacting with AD and other neuropathologies. Recent neuroimaging data have improved our understanding of the etiology of VCD. Symptomatic treatments for VaD have modest benefit and there is increased focus on the primary and secondary preventative benefits of vascular risk factor control.

Relationship Between Brain Arterial Pathology and Neurocognitive Performance Among Individuals With Human Immunodeficiency Virus.

Background: Human immunodeficiency virus-positive (HIV+) individuals have higher rates of cognitive impairment and cerebrovascular disease compared with uninfected populations. We hypothesize that cerebrovascular disease, specifically brain large artery disease, may play a role in HIV-associated neurocognitive disorders (HAND). Methods: Participants (N = 94) in the Manhattan HIV Brain Bank study were followed on average 32 ± 33 months with repeated neuropsychological examinations until death. We used five cognitive domains (motor, processing speed, working memory, verbal fluency, and executive functioning) to assess ante mortem performance. We quantified the diameter of the lumen and arterial wall thickness obtained during autopsy. The diagnoses of HAND were attributed using the American Academy of Neurology nosology. We used generalized linear mixed model to account for repeated measures, follow-up time, and codependence between arteries. Models were adjusted for demographics, viral loads, CD4 counts, history of opportunistic infections, and vascular risks. Results: We included 94 HIV+ individuals (mean age 56 ± 8.3, 68% men, 54% African American). In adjusted models, there was an association between arterial wall thickness and global cognitive score (B = -0.176, P value = .03), processing speed (B = -0.175, P = .05), and verbal fluency (B = -0.253, P = .02). Participants with incident or worsening HAND had thicker brain arterial walls (B = 0.523 ± 0.234, P = .03) and smaller arterial lumen (B = -0.633 ± 0.252, P = .01). Conclusions: We report here a novel association between brain arterial wall thickening and poorer ante mortem cognitive performance and diagnosis of incident or worsening HAND at death. Strategies to preserve the arterial lumen or to prevent wall thickening may impact HAND.

Postmortem Study Exploring Distribution and Patterns of Intracranial Artery Calcification.

Background and Purpose- Intracranial artery calcification detected by computed tomography is associated with ischemic stroke as an indicator of intracranial atherosclerosis. However, little is known about its histopathology. This study aimed to explore the intracranial calcification patterns and their associations with atherosclerotic plaques. Methods- We recruited 32 adult autopsy cases to assess the calcification patterns and distributions in the middle cerebral artery, vertebral artery, and basilar artery. The relationships of calcification patterns with plaque phenotype and luminal stenosis were evaluated. The calcification patterns on computed tomography were correlated with that on histology. Results- Visible calcifications were detected within 37 (39%) segments, including 25 segments with intimal calcification, 6 segments with internal elastic lamina calcification, 3 segments with adventitial calcification, and 3 segments with concurrent calcification. Calcification occurred more often in the vertebral artery (51%), followed by the middle cerebral artery (35%) and basilar artery (14%; P<0.01 for vertebral artery versus basilar artery). Internal elastic lamina calcification was predominantly detected in the vertebral artery (7/8, 88%). All of the 27 (100%) intimal calcifications were present in the progressive atherosclerotic lesions ( P<0.001), whereas only 3/8 (38%) internal elastic lamina calcifications and 4/6 (67%) adventitial calcifications were associated with progressive plaques. Arteries with intimal calcification had more severe luminal stenosis than those without (46% versus 21%; P<0.001). Conclusions- Our histological findings indicate that the presence of intracranial artery calcification has 3 patterns, including intimal, internal elastic lamina, and adventitial calcifications. But only intimal calcification is related with progressive atherosclerotic lesions, indicative of a proxy for intracranial atherosclerosis.

Three-dimensional black blood contrast enhanced magnetic resonance imaging in patients with acute ischemic stroke and negative susceptibility vessel sign.

PURPOSE: The purpose of this study was to evaluate the enhancement patterns of three-dimensional (3D) black blood (BB) contrast enhanced magnetic resonance (MR) imaging in acute stroke patients with negative susceptibility vessel sign (SVS). MATERIALS AND METHODS: From January 2014 to August 2016 we retrospectively reviewed MR imaging and MR angiography findings of patients who presented with acute stroke symptoms of less than 24 h duration. For the 394 patients enrolled, we assessed the frequency of patients who exhibited negative SVS on susceptibility weighted MR imaging (SWI) and positive enhancement in 3D BB contrast enhanced MR imaging. We subdivided the enrolled group according to whether the MR angiography findings suggested stenosis (stenosis group) or occlusion (occlusion group). Enhancement patterns on BB contrast enhanced MR imaging were compared between the two groups according to several qualitative parameters: intensity (weak or strong), morphology (linear/eccentric or round/concentric), length (focal or segmental) and multiplicity (single or multiple). RESULTS: Sixty-two of 394 patients (15.7%) showed positive findings on BB contrast-enhanced MR imaging with negative SVS. Forty-two patients were classified into the stenosis group, and 20 patients were assigned to the occlusion group. Enhancement patterns of the stenosis group showed weak intensity, linear or eccentric morphology and focal lesion length on BB contrast enhanced MR imaging, compared to the occlusion group (P < 0.001). In contrast, enhancement patterns of the occlusion group showed strong intensity, round or concentric morphology and longer segmental lesion length, compared to the stenosis group (P < 0.001). CONCLUSION: Three-dimensional BB contrast enhanced MR imaging in acute stroke patients with stenotic lesions and negative SVS shows enhancement patterns of linear or eccentric morphology and shorter, more focal lesions.

Intracranial Arterial Calcification in Black Africans with Acute Ischaemic Stroke.

BACKGROUND: Intracranial arterial calcification (IAC), a recognized marker of atherosclerosis on cranial computed tomography (CT), is an independent risk factor for ischaemic stroke. This study aimed to determine the prevalence, distribution, severity, and associations of IAC in adults with acute ischaemic stroke (AIS) at the University College Hospital, Ibadan, Nigeria. METHODS: Cranial CT images of 130 consecutive adults who presented with AIS were acquired on a 64-slice multi-detector Toshiba Aquilion scanner and evaluated for IAC in bone window on Vitrea® software using a semi-quantitative scoring method for extent, thickness, and length of calcifications in the large intracranial arteries. Associations of IAC with clinical and laboratory data were determined by statistical analysis at p < 0.05. RESULTS: There were 71 males (54.6%), and the mean age of all patients was 63.0 ± 13.2 years. Hypertension was the most common risk factor (83.1%). IAC was found in 121 patients (93.1%), predominantly in the carotid siphon (86.1%) followed by the intracranial vertebral arteries (9.3%), middle cerebral arteries (2.4%), basilar artery (1.2%), and the anterior cerebral arteries (1%). The burden of IAC ranged from mild (17.4%) to moderate (52.1%) to severe (30.6%). Age (p < 0.001), diastolic blood pressure (p = 0.037), and alcohol use (0.046) were significantly different among the patients with mild, moderate, and severe degrees of IAC. IAC was associated with age (p < 0.001), hypertension (p = 0.03), diabetes mellitus (p = 0.02), hyperlipidaemia (p = 0.04), and alcohol use (p < 0.001) but not with sex (p = 0.35). CONCLUSIONS: The burden of IAC is very high among native African patients with AIS and preferentially involves proximal inflow arteries. Therefore, the role of large vessel atherosclerosis in ischaemic stroke in native Africans should be explored in future multinational, multimodality studies.

Post-varicella Arterial Ischemic Stroke in Denmark 2010 to 2016.

BACKGROUND: Varicella, most often a benign disease of childhood, is associated with an increased risk of arterial ischemic stroke in children. The aim of the present study was to estimate the incidence of post-varicella arterial ischemic stroke in the Danish child population and describe clinical characteristics of children admitted with post-varicella arterial ischemic stroke. METHODS: In the Danish National Patient Register, we identified inpatients 28 days to 16 years of age with a discharge diagnosis of stroke or cerebrovascular disease from 2010 to 2016. Medical files were reviewed, and children with arterial ischemic stroke and varicella infection less than 12 months before onset of symptoms were included. RESULTS: We identified 15 children with arterial ischemic stroke and varicella less than 12 months before. In nine children, the diagnosis was confirmed by detection of varicella zoster virus DNA or varicella zoster virus immunoglobulin G in the cerebrospinal fluid. All children were previously healthy, the mean age was four years, and 67% were male. The median time from varicella rash to arterial ischemic stroke was 4.6 months. The most common location of arterial ischemic stroke was the basal ganglia, and affected vessels were most often in the anterior circulation. Fifty-three percent experienced neurological sequelae of varying degree. CONCLUSIONS: In Denmark, where varicella vaccination is not part of the childhood vaccination program, the estimated risk of post-varicella arterial ischemic stroke was one case (including possible cases) per 26,000 children with varicella.

The Contrast Enhancement of Intracranial Arterial Wall on High-resolution MRI and Its Clinical Relevance in Patients with Moyamoya Vasculopathy.

The purpose of this study is to investigate the characteristics of intracranial vessel wall enhancement and its relationship with ischemic infarction in patients with Moyamoya vasculopathy (MMV). Forty-seven patients with MMV confirmed by angiography were enrolled in this study. The vessel wall enhancement of the distal internal carotid artery, anterior cerebral artery and middle cerebral artery was classified into eccentric and concentric patterns, as well as divided into three grades: grade 0, grade 1 and grade 2. The relationship between ischemic infarction and vessel wall enhancement was also determined. Fifty-six enhanced lesions were found in patients with (n = 25) and without acute infarction (n = 22). The incidence of lesions with grade 2 enhancement in patients with acute infarction was greater than that in those without acute infarction (p = 0.011). In addition, grade 2 enhancement of the intracranial vessel wall was significantly associated with acute ischemic infarction (Odds ratio, 26.7; 95% confidence interval: 2.8-258.2; p = 0.005). Higher-grade enhancement of the intracranial vessel wall is independently associated with acute ischemic infarction in patients with MMV. The characteristics of intracranial vessel wall enhancement may serve as a marker of its stability and provide important insight into ischemic stroke risk factors.

Evaluation of fast highly undersampled contrast-enhanced MR angiography (sparse CE-MRA) in intracranial applications - initial study.

OBJECTIVES: To assess the image quality of sparsely sampled contrast-enhanced MR angiography (sparse CE-MRA) providing high spatial resolution and whole-head coverage. MATERIALS AND METHODS: Twenty-three patients scheduled for contrast-enhanced MR imaging of the head, (N = 19 with intracranial pathologies, N = 9 with vascular diseases), were included. Sparse CE-MRA at 3 Tesla was conducted using a single dose of contrast agent. Two neuroradiologists independently evaluated the data regarding vascular visibility and diagnostic value of overall 24 parameters and vascular segments on a 5-point ordinary scale (5 = very good, 1 = insufficient vascular visibility). Contrast bolus timing and the resulting arterio-venous overlap was also evaluated. Where available (N = 9), sparse CE-MRA was compared to intracranial Time-of-Flight MRA. RESULTS: The overall rating across all patients for sparse CE-MRA was 3.50 ± 1.07. Direct influence of the contrast bolus timing on the resulting image quality was observed. Overall mean vascular visibility and image quality across different features was rated good to intermediate (3.56 ± 0.95). The average performance of intracranial Time-of-Flight was rated 3.84 ± 0.87 across all patients and 3.54 ± 0.62 across all features. CONCLUSION: Sparse CE-MRA provides high-quality 3D MRA with high spatial resolution and whole-head coverage within short acquisition time. Accurate contrast bolus timing is mandatory. KEY POINTS: • Sparse CE-MRA enables fast vascular imaging with full brain coverage. • Volumes with sub-millimetre resolution can be acquired within 10 seconds. • Reader's ratings are good to intermediate and dependent on contrast bolus timing. • The method provides an excellent overview and allows screening for vascular pathologies.

Intracranial vessel wall imaging for evaluation of steno-occlusive diseases and intracranial aneurysms.

Cerebrovascular diseases have traditionally been classified, diagnosed and managed based on their luminal characteristics. However, over the past several years, several advancements in MRI techniques have ushered in high-resolution vessel wall imaging (HR-VWI), enabling evaluation of intracranial vessel wall pathology. These advancements now allow us to differentiate diseases which have a common angiographic appearance but vastly different natural histories (i.e. moyamoya versus atherosclerosis, reversible cerebral vasoconstriction syndrome versus vasculitis, stable versus unstable intracranial aneurysms). In this review, we detail the anatomical, histopathological and imaging characteristics of various intracranial steno-occlusive diseases and types of intracranial aneurysms and describe the role that HR-VWI can play in diagnosis, risk stratification and treatment.

Decreased muscle mass in Korean subjects with intracranial arterial stenosis: The Kangbuk Samsung Health Study.

BACKGROUNDS AND AIMS: Intracranial arterial stenosis (ICAS) is a common cause of ischemic stroke in Asians. Decreased muscle mass is one of the major causes of chronic disease in adults. The purpose of this study was to analyze the relationship between muscle mass and ICAS in Korean adults. METHODS: For this study, we selected a total of 10,530 participants (mean age, 43.3 years; 8558 men) in a health screening program, for whom transcranial Doppler (TCD) ultrasound was used to detect >50% ICAS based on criteria modified from the stroke outcomes and neuroimaging of intracranial atherosclerosis trial. Body composition was evaluated by bioelectrical impedance analysis (BIA). Skeletal muscle index (SMI) was calculated with muscle mass/weight (kg) * 100. RESULTS: Among the total patient population, 322 (3.1%) subjects had ICAS. Subjects with ICAS were older, and had higher mean values for fasting glucose, body mass index and blood pressure compared with those without ICAS. Subjects with ICAS had significantly lower muscle mass, SMI and higher percent body fat compared with those without ICAS. In logistic regression analysis, the subjects in the highest tertile of muscle mass had the lowest odds ratio for ICAS with the lowest tertile group of muscle mass as the reference group even after adjusting for age, systolic blood pressure, fasting blood glucose, sex, smoking and exercise (OR 0.650, 95% CI 0.442-0.955). CONCLUSIONS: Subjects with ICAS had significantly decreased muscle mass compared with those without ICAS in Korean adults. The risk for ICAS was lower in subjects with higher muscle mass.

Pathogenesis and neuroimaging of cerebral large and small vessel disease in type 2 diabetes: A possible link between cerebral and retinal microvascular abnormalities.

Diabetes patients have more than double the risk of ischemic stroke compared with non-diabetic individuals, and its neuroimaging characteristics have important clinical implications. To understand the pathophysiology of ischemic stroke in diabetes, it is important to focus not only on the stroke subtype, but also on the size and location of the occlusive vessels. Specifically, ischemic stroke in diabetes patients might be attributed to both large and small vessels, and intracranial internal carotid artery disease and small infarcts of the posterior circulation often occur. An additional feature is that asymptomatic lacunar infarctions are often seen in the basal ganglia and brain stem on brain magnetic resonance imaging. In particular, cerebral small vessel disease (SVD), including lacunar infarctions, white matter lesions and cerebral microbleeds, has been shown to be associated not only with stroke incidence, but also with the development and progression of dementia and diabetic microangiopathy. However, the pathogenesis of cerebral SVD is not fully understood. In addition, data on the association between neuroimaging findings of the cerebral SVD and diabetes are limited. Recently, the clinical importance of the link between cerebral SVD and retinal microvascular abnormalities has been a topic of considerable interest. Several clinical studies have shown that retinal microvascular abnormalities are closely related to cerebral SVD, suggesting that retinal microvascular abnormalities might be pathophysiologically linked to ischemic cerebral SVD. We review the literature relating to the pathophysiology and neuroimaging of cerebrovascular disease in diabetes, and discuss the problems based on the concept of cerebral large and small vessel disease.

The Number of Stenotic Intracranial Arteries Is Independently Associated with Ischemic Stroke Severity.

BACKGROUND: The severity of ischemic stroke symptoms varies among patients and is a critical determinant of patient outcome. To date, the association between the number of stenotic intracranial arteries and stroke severity remains unclear. AIMS: We aimed to investigate the association between the number of stenotic major intracranial arteries (NSMIA) and ischemic stroke severity, as well as the degree of stenosis and common stroke risk factors. METHODS: We performed a retrospective analysis of patients with digital subtraction angiography (DSA)-confirmed ischemic stroke. Clinical stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). The number of stenotic vessels was counted from the internal carotid arteries and vertebral arteries, bilaterally. RESULTS: Eighty three patients were recruited from a single center and included in the study. NSMIA was significantly correlated with stroke severity (Pearson Correlation Coefficient = 0.485, P < 0.001), but not with the degree of stenosis (Pearson Correlation Coefficient = 0.01, P = 0.90). Multivariate regression analysis revealed that NSMIA was significantly associated with the NIHSS score after adjusting for stroke risk factors. The adjusted odds ratio (per lateral) was 2.092 (95% CI, 0.865 to 3.308, P = 0.001). The degree of stenosis was also significantly associated with the NIHSS score after adjusting for common risk factors. The odds ratio (per 10%) was 0.712 (95% CI, 0.202 to 1.223, P = 0.007). CONCLUSIONS: The number of stenotic intracranial major arteries is associated with the severity of ischemic stroke independent of the degree of stenosis and other stroke risk factors. To the best of our knowledge, this has not been previosuly studied in great detail using DSA. Our data highlight the importance of examining all major arteries in stroke patients.

Detection of Cerebral Vasculopathy by Transcranial Doppler in Children With Neurofibromatosis Type 1.

Neurofibromatosis type 1 is characterized by nerve sheath neurofibromas associated with a number of additional clinical features, including cerebrovascular disease. The aim of this study was to use transcranial Doppler as a screening method for identifying cerebral vasculopathy in children with neurofibromatosis type 1. Forty children with neurofibromatosis type 1, aged 5 to 18 years old, were examined by transcranial Doppler. Patients presenting with hemodynamic features of arterial stenosis/occlusion on transcranial Doppler underwent magnetic resonance angiography to confirm the findings. Magnetic resonance angiography was performed on 4 children who exhibited a transcranial Doppler hemodynamic pattern indicative of cerebral vasculopathy. Among these cases, 2 presented internal carotid artery stenosis/occlusion, 1 had bilateral middle cerebral artery stenosis, and 1 presented a normal magnetic resonance angiography result. Transcranial Doppler can be used routinely in the investigation of cerebrovascular disease in neurofibromatosis type 1 patients, where magnetic resonance angiography can be subsequently applied to confirm the diagnosis, further contributing to the prevention of cerebrovascular events.