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Neurology Aug 2023Assessing the risk of recurrent intracerebral hemorrhage (ICH) is of high clinical importance. MRI-based cerebral small vessel disease (SVD) markers may help establish...
BACKGROUND AND OBJECTIVES
Assessing the risk of recurrent intracerebral hemorrhage (ICH) is of high clinical importance. MRI-based cerebral small vessel disease (SVD) markers may help establish ICH etiologic subtypes (including cryptogenic ICH) relevant for recurrence risk.
METHODS
We investigated the risk of recurrent ICH in a large cohort of consecutive ICH survivors with available MRI at baseline. Patients with macrovascular, structural, or other identified secondary causes (other than SVD) were excluded. Based on MRI findings, ICH etiology was defined as probable cerebral amyloid angiopathy (CAA) according to the Boston 2.0 criteria, arteriolosclerosis (nonlobar ICH and additional markers of arteriolosclerosis, absent lobar hemorrhagic lesions), mixed SVD (mixed deep and lobar hemorrhagic changes), or cryptogenic ICH (no MRI markers of SVD). Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. Data from an independent multicenter cohort (CROMIS-2 ICH) were used to confirm core findings.
RESULTS
Of 443 patients with ICH (mean age 67 ± 13 years, 41% female), ICH etiology was mixed SVD in 36.7%, arteriolosclerosis in 23.6%, CAA in 23.0%, and cryptogenic ICH in 16.7%. During a median follow-up period of 5.7 years (interquartile range 2.9-10.0, 2,682 patient-years), recurrent ICH was found in 59 individual patients (13.3%). The highest recurrence rate per 100 person-years was detected in patients with CAA (8.5, 95% CI 6.1-11.7), followed by that in those with mixed SVD (1.8, 95% CI 1.1-2.9) and arteriolosclerosis (0.6, 95% CI 0.3-1.5). No recurrent ICH occurred in patients with cryptogenic ICH during 510 person-years follow-up (97.5% CI 0-0.7); this finding was confirmed in an independent cohort (CROMIS-2 ICH, n = 216), in which also there was no recurrence in patients with cryptogenic ICH. In patients with CAA, cortical superficial siderosis was the imaging feature strongest related to ICH recurrence (hazard ratio 5.7, 95% CI 2.4-13.6).
DISCUSSION
MRI-based etiologic subtypes are helpful in determining the recurrence risk of ICH; while the highest recurrence risk was found in CAA, recurrence risk was low for arteriolosclerosis and negligible for cryptogenic ICH.
Topics: Humans; Female; Middle Aged; Aged; Aged, 80 and over; Male; Arteriolosclerosis; Cerebral Hemorrhage; Magnetic Resonance Imaging; Cerebral Amyloid Angiopathy; Cerebral Small Vessel Diseases
PubMed: 37349111
DOI: 10.1212/WNL.0000000000207510 -
Journal of Clinical Neuroscience :... Jul 2013Cerebral microbleeds (CMB) are small haemosiderin deposits, detected with varying sensitivity by specific MRI sequences. CMB prevalence increases most clearly and... (Review)
Review
Cerebral microbleeds (CMB) are small haemosiderin deposits, detected with varying sensitivity by specific MRI sequences. CMB prevalence increases most clearly and reliably with age, but CMB are also associated with various acquired and heritable cerebral vasculopathies (most commonly arteriolosclerosis and amyloid angiopathy). CMB often coincide with the other radiological features of small vessel disease, cortical microinfarction, lacunar infarction and periventricular white matter hyperintensity. CMB distribution may suggest an underlying cause; in particular, lobar-restricted or corticosubcortical CMB suggest amyloid angiopathy. In both ischaemic stroke and intracerebral haemorrhage, CMB appear to be a marker of underlying vasculopathy severity, and therefore a predictor of recurrence. Although CMB are also associated with several broad clinical neurological impairments (cognitive impairment, depression and gait instability), it is debatable whether CMB themselves are causative. The clinical implications of CMB detection remain unclear. Thrombolysis for ischaemic stroke is not contraindicated. It is uncertain whether more conservative antithrombotic strategies are warranted if CMB are detected in patients with symptomatic vascular disease or atrial fibrillation. Studies (observational and randomized) of various treatment strategies in patients with CMB and these concomitant conditions are required to resolve these treatment dilemmas.
Topics: Cerebral Hemorrhage; Cerebrovascular Disorders; Humans
PubMed: 23707603
DOI: 10.1016/j.jocn.2012.12.002 -
Archives of Pathology & Laboratory... Aug 2009Arteriosclerosis is the vascular disease that is the leading cause of mortality in industrialized countries. Currently, there are 3 lesions within the broader category... (Review)
Review
CONTEXT
Arteriosclerosis is the vascular disease that is the leading cause of mortality in industrialized countries. Currently, there are 3 lesions within the broader category of arteriosclerosis: atherosclerosis, Mönckeberg medial calcific sclerosis, and arteriolosclerosis.
OBJECTIVE
In this review, we discuss the history of the terminology and current classification of arteriosclerosis and problems with the current classification. We also discuss recently described new arterial lesions that are not in the current classification.
DATA SOURCES
In spite of the prevalence and importance of arteriosclerotic vascular disease, and the widespread use of the current terminology, there are major problems with the current classification: (1) the current classification has an inconsistent naming convention, (2) the classification fails to use terms that accurately describe the lesions, and (3) important arterial lesions are absent from the classification. In addition, although the terms arteriosclerosis and atherosclerosis describe different lesions, these terms are often used interchangeably.
CONCLUSION
Consideration should be given for a new more inclusive and accurate classification of "arteriosclerotic" lesions that more accurately reflects the pathology of these important vascular lesions.
Topics: Arteries; Arteriosclerosis; Humans; Terminology as Topic
PubMed: 19653731
DOI: 10.5858/133.8.1309 -
Annals of Neurology Jan 2023Determining the underlying causes of intracerebral hemorrhage (ICH) is of major importance, because risk factors, prognosis, and management differ by ICH subtype. We...
OBJECTIVE
Determining the underlying causes of intracerebral hemorrhage (ICH) is of major importance, because risk factors, prognosis, and management differ by ICH subtype. We developed a new causal CLASsification system for ICH Subtypes, termed CLAS-ICH, based on recent advances in neuroimaging.
METHODS
CLAS-ICH defines 5 ICH subtypes: arteriolosclerosis, cerebral amyloid angiopathy, mixed small vessel disease (SVD), other rare forms of SVD (genetic SVD and others), and secondary causes (macrovascular causes, tumor, and other rare causes). Every patient is scored in each category according to the level of diagnostic evidence: (1) well-defined ICH subtype; (2) possible underlying disease; and (0) no evidence of the disease. We evaluated CLAS-ICH in a derivation cohort of 113 patients with ICH from Massachusetts General Hospital, Boston, USA, and in a derivation cohort of 203 patients from Inselspital, Bern, Switzerland.
RESULTS
In the derivation cohort, a well-defined ICH subtype could be identified in 74 (65.5%) patients, including 24 (21.2%) with arteriolosclerosis, 23 (20.4%) with cerebral amyloid angiopathy, 18 (15.9%) with mixed SVD, and 9 (8.0%) with a secondary cause. One or more possible causes were identified in 42 (37.2%) patients. Interobserver agreement was excellent for each category (kappa value ranging from 0.86 to 1.00). Despite substantial differences in imaging modalities, we obtained similar results in the validation cohort.
INTERPRETATION
CLAS-ICH is a simple and reliable classification system for ICH subtyping, that captures overlap between causes and the level of diagnostic evidence. CLAS-ICH may guide clinicians to identify ICH causes, and improve ICH classification in multicenter studies. ANN NEUROL 2023;93:16-28.
Topics: Humans; Arteriolosclerosis; Cerebral Hemorrhage; Cerebral Amyloid Angiopathy; Risk Factors; Neuroimaging; Magnetic Resonance Imaging
PubMed: 36197294
DOI: 10.1002/ana.26519 -
Alzheimer Disease and Associated... 1991Analysis of the pathology of multi-infarct dementia is best carried out using a two-axis approach. The first axis describes the tissue damage, classified as... (Review)
Review
Analysis of the pathology of multi-infarct dementia is best carried out using a two-axis approach. The first axis describes the tissue damage, classified as macroinfarcts, cortical microinfarcts, basal ganglionic lacunes, white matter lacunes, dilated perivascular spaces, diffuse white matter rarefaction, and perivascular edema. The second axis describes the vascular abnormalities, classified as atherosclerosis involving the extracranial or intracranial arteries, arteriolosclerosis, congophilic angiopathy, emboli, and no structural abnormality. Multiple infarcts and white matter rarefaction are commonly seen as a component of Alzheimer disease, in keeping with the development of congophilic angiopathy and possibly other vascular changes in the latter disease. Evidence is presented to support the concept that the white matter rarefaction of Alzheimer disease and aging is associated with perivascular edema, rather than partial infarction.
Topics: Age Factors; Aged; Alzheimer Disease; Brain; Cerebral Cortex; Dementia, Multi-Infarct; Humans; Intracranial Arteriosclerosis
PubMed: 2059411
DOI: 10.1097/00002093-199100520-00005 -
American Journal of Hypertension Mar 2005We present the hypothesis that most cases of essential hypertension occur via two phases. The first phase is initiated by episodes of renal vasoconstriction induced by a... (Review)
Review
We present the hypothesis that most cases of essential hypertension occur via two phases. The first phase is initiated by episodes of renal vasoconstriction induced by a hyperactive sympathetic nervous system, activation of the renin-angiotensin system, or hyperuricemia resulting from diet or genetics. During this phase the hypertension is salt resistant and renin dependent, and the kidney normal. Over time, preglomerular vascular disease develops (arteriolosclerosis), associated with tubulointerstitial inflammation; this shifts the hypertension to a salt-sensitive, volume-dependent, and renal-dependent pathway. This pathway unites many of the previous hypotheses on the etiology of hypertension, and offers insights into ways to prevent, ameliorate, or cure the underlying process.
Topics: Animals; Humans; Hypertension, Renal; Hyperuricemia; Oxidative Stress
PubMed: 15797666
DOI: 10.1016/j.amjhyper.2004.08.035 -
Journal of Hypertension. Supplement :... Jun 2002The vast majority of patients with essential hypertension have structural changes in their kidneys consisting of preglomerular vascular disease ('arteriolosclerosis')... (Review)
Review
The vast majority of patients with essential hypertension have structural changes in their kidneys consisting of preglomerular vascular disease ('arteriolosclerosis') and tubulointerstitial injury. Most authorities have assumed that these structural changes occur secondary to hypertensive renal injury. However, Goldblatt proposed that primary renal microvascular disease might be the cause of some forms of hypertension. In this paper we present recent studies from our group that support a role for both preglomerular vascular disease as well as the tubulointerstitial inflammatory response in mediating salt-sensitivity. We propose that subtle acquired renal injury may underlie the etiology of some forms of salt-sensitive hypertension.
Topics: Animals; Humans; Hypertension; Ischemia; Kidney; Kidney Diseases; Nephrons; Sodium Chloride; Vascular Diseases
PubMed: 12184051
DOI: No ID Found -
Archives of Pathology & Laboratory... Mar 2013Nodular, intercapillary glomerulosclerotic lesions resembling Kimmelstiel-Wilson nodules commonly observed in diabetic nephropathy can also be seen in patients without... (Review)
Review
CONTEXT
Nodular, intercapillary glomerulosclerotic lesions resembling Kimmelstiel-Wilson nodules commonly observed in diabetic nephropathy can also be seen in patients without any clinical history or evidence of diabetes.
OBJECTIVES
To discuss the pathobiology of lesions reminiscent of diabetes nephropathy, including light-chain deposition disease, amyloidosis, immunotactoid nephropathy, the membranoproliferative form of glomerulonephritis, and idiopathic nodular glomerulosclerosis, and how to differentiate them from diabetic nephropathy.
DATA SOURCES
Published literature and authors' personal experience.
CONCLUSIONS
The well-formed, intercapillary, nodular mesangial lesions, along with thickened glomerular basement membranes and tubular basement membranes, and hyaline arteriolosclerosis are virtually pathognomic of diabetic nephropathy. However, the pathologist must exclude lesions reminiscent of diabetic nephropathy by performing special stains on histologic sections, immunofluorescence, and electron microscopic studies.
Topics: Diabetic Nephropathies; Humans; Kidney
PubMed: 23451746
DOI: 10.5858/arpa.2012-0243-RA -
Journal of Neuropathology and... Feb 2022Cerebral small vessel disease (SVD) causes lacunar stroke and vascular cognitive impairment in older people. The pathogenic pathways from vessel pathology to parenchymal...
Cerebral small vessel disease (SVD) causes lacunar stroke and vascular cognitive impairment in older people. The pathogenic pathways from vessel pathology to parenchymal damage in SVD are unknown. Neurofilaments are axonal structural proteins. Neurofilament-light (NfL) is an emerging biomarker for neurological disease. Here, we examined the high molecular weight form neurofilament-heavy (NfH) and quantified a characteristic pattern of peri-arterial (vasculocentric) NfH labeling. Subcortical frontal and parietal white matter from young adult controls, aged controls, and older people with SVD or severe Alzheimer disease (n = 52) was immunohistochemically labeled for hyperphosphorylated NfH (pNfH). The extent of pNfH immunolabeling and the degree of vasculocentric axonal pNfH were quantified. Axonal pNfH immunolabeling was sparse in young adults but a common finding in older persons (controls, SVD, or AD). Axonal pNfH was often markedly concentrated around small penetrating arteries. This vasculocentric feature was more common in older people with SVD than in those with severe AD (p = 0.004). We conclude that axonal pNfH is a feature of subcortical white matter in aged brains. Vasculocentric axonal pNfH is a novel parenchymal lesion that is co-located with SVD arteriopathy and could be a consequence of vessel pathology.
Topics: Aged; Aged, 80 and over; Biomarkers; Brain; Cerebral Small Vessel Diseases; Humans; Intermediate Filaments; White Matter
PubMed: 35086142
DOI: 10.1093/jnen/nlab134 -
Acta Neuropathologica Mar 2022Emerging evidence suggests that small vessel disease (SVD) is a risk factor for clinical dementia and may contribute to AD neuropathological changes. Watershed brain...
Emerging evidence suggests that small vessel disease (SVD) is a risk factor for clinical dementia and may contribute to AD neuropathological changes. Watershed brain regions are located at the most distal areas between arterial territories, making them vulnerable to SVD-related changes. We examined the association of pathologic markers of SVD, specifically arteriolosclerosis in watershed brain regions, with AD pathologic changes. Participants (N = 982; mean age-at-death = 90; 69% women) were enrolled as part of one of two cohort studies of aging and dementia. At autopsy, neuropathological evaluation included semi-quantitative grading of arteriolosclerosis pathology from 2 cortical watershed regions: the anterior watershed (AWS) and posterior watershed (PWS), densities for cortical β-amyloid and tau-tangle pathology, and other common age-related pathologies. Linear regression models examined the association of watershed arteriolosclerosis pathology with β-amyloid and tau-tangle burden. In follow-up analyses, available ex-vivo MRI and proteomics data in a subset of decedents were leveraged to examine the association of whole brain measure of WMH, as a presumed MRI marker of SVD, with β-amyloid and tau-tangle burden, as well as to examine the association of watershed arteriolosclerosis with proteomic tau. Watershed arteriolosclerosis was common, with 45% of older persons having moderate-to-severe arteriolosclerosis pathology in the AWS region, and 35% in the PWS. In fully adjusted models that controlled for demographics and common age-related pathologies, an increase in severity of PWS arteriolosclerosis was associated with a higher burden of tau-tangle burden, specifically neocortical tau burden, but not with β-amyloid. AWS arteriolosclerosis was not associated with β-amyloid or tau pathology. Ex-vivo WMH was associated with greater tau-tangle pathology burden but not β-amyloid. Furthermore, PWS arteriolosclerosis was associated with higher abundance of tau phosphopeptides, that promote formation of tau aggregates. These data provide compelling evidence that SVD, specifically posterior watershed arteriolosclerosis pathology, is linked with tau pathological changes in the aging brain.
Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Amyloid beta-Peptides; Brain; Female; Humans; Male; Proteomics; tau Proteins
PubMed: 35044500
DOI: 10.1007/s00401-021-02397-x