Leukoaraiosis: From an Ancient Term to an Actual Marker of Poor Prognosis
2008; Lippincott Williams & Wilkins; Volume: 39; Issue: 5 Linguagem: Inglês
10.1161/strokeaha.107.505602
ISSN1524-4628
Autores Tópico(s)Parasites and Host Interactions
ResumoHomeStrokeVol. 39, No. 5Leukoaraiosis: From an Ancient Term to an Actual Marker of Poor Prognosis Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBLeukoaraiosis: From an Ancient Term to an Actual Marker of Poor Prognosis Leonardo Pantoni Leonardo PantoniLeonardo Pantoni From the Department of Neurological and Psychiatric Sciences, University of Florence, Italy. Originally published13 Mar 2008https://doi.org/10.1161/STROKEAHA.107.505602Stroke. 2008;39:1401–1403Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: March 13, 2008: Previous Version 1 See related article, pages 1409–1413.The term leukoaraiosis (from the Greek leuko, white, and araiosis, rarefaction) was introduced in 1986 by Hachinski, Potter and Merskey to designate bilateral and symmetrical areas in the periventricular and centrum semiovale white matter that appeared hypodense on CT scans and hyperintense on T2-weighted MRI.1,2 Leukoaraiosis was supposed to be "a neutral term, exact enough to define white-matter changes, sufficient as a description or label, and demanding enough to require precise clinical and imaging descriptions."1,2 It was clear in Hachinski and coworkers' proposal the aim of contrasting the tendency to immediately identify a radiological aspect with a clinical picture. At that time, changes or lesions of the white matter were recognized with increasing frequency on the brain CT scans of elderly patients,3 and some authors had begun to attribute a clinical significance to these radiological findings, particularly interpreting them as a correlate of cognitive decline. According to some, the introduction of CT had made possible the identification in vivo of subcortical arteriosclerotic encephalopathy (or Binswanger disease), a form of vascular dementia with only few cases reported on pathological grounds until the eighties.4,5 The issue became even more complex after the introduction of MRI in neurological clinical practice because it was soon apparent that this neuroimaging technique was able to detect cerebral white matter changes with much higher frequency than CT.6,7 On MRI, changes of the white matter can be detected even when they are of very small ("puntiform") size.8 A review of the topic published in 1995 concluded that the clinical significance of leukoaraiosis remained incompletely defined, but it also suggested that the presence of the most severe degrees of these changes had an effect on cognitive functions in subjects without or with only minor cognitive impairment.9 The number of studies from which these conclusions were drawn at that time was much smaller than that available today.9Over the last 10 years, evidence has been mounting on the prevalence, clinical significance, and prognostic value of white matter changes (Table). Nowadays, we know that minimal changes are almost invariably found in the general population.10,11 Data are sufficient to sustain that the mildest degree of leukoaraiosis is to be considered as an almost normal finding in the brain of elderly patients. However, evidence has also accumulated showing that moderate-to-severe white matter changes are not so benign. They are in fact correlated with motor and gait disturbances,12 depressive symptoms,13 urinary disturbances,14 and some cognitive deficits15; the extent of these latter, however, is likely also influenced by possibly associated lesions such as lacunar infarcts and coexisting degenerative diseases.16–19 Longitudinal studies have outlined also a predictive role of leukoaraiosis in terms of less favorable prognosis in the general population and in a number of clinical conditions (Table). It is therefore essential in studies on white matter changes to abandon the mere assessment of their presence, and it is crucial to recognize their most severe degrees because these are likely the ones bearing clinical consequences. Further studies are needed to determine whether mild-to-moderate changes progress over time to become severe. Most of the studies with a longitudinal assessment of leukoaraiosis, however, have found that the most powerful predictor of progression is indeed baseline leukoaraiosis severity.20,21 Should this be definitely confirmed in the future, it will strongly support the hypothesis that at least 2 different pathological age-related processes of the white matter exist: a first one, more benign and attributable to a quasi-physiological aging process of the brain; and a second one, clearly pathological and associated with clinical disturbances and disease status. This will eventually demonstrate Hachinski and coworkers' original hypothesis on the heterogeneity of leukoaraiosis.2 Preventive and therapeutic measures will obviously have to focus on the second type of leukoaraiosis. Table. Some of the Clinical Correlates and Prognostic Significance of White Matter Changes (Leukoaraiosis)Clinical correlates (cross-sectional studies) Cognitive deficits (particularly in terms of speed of mental processing, attention, and executive functions) Impaired mobility and balance, disturbances of gait Mood disturbances and depressive symptoms Urinary incontinence Decreased activity of daily living functionalityPrognostic significance (follow-up studies) Increased risk of small-vessel strokes Increased risk of vascular mortality Increased risk of bleeding in patients on anticoagulation Increased risk of bleeding in patients undergoing cerebral thrombolysis Increased surgical risk in patients undergoing carotid artery surgery Poorer clinical outcome in patients with infratentorial strokes Increased risk of dementia (in the general population) Increased risk of dementia (in stroke patients) Increased risk of transition to disabilityPerhaps, the most important result in recent years has been the demonstration that leukoaraiosis represents a marker of poor prognosis, particularly in terms of increased mortality and risk of dementia.22–24 In a multicenter study, the severity of white matter changes at baseline was an independent predictor of the transition from a normal functional status to disability already after 1 year.25 The same study showed that this transition was mainly explained by cognitive and motor performances decline. This is of relevance because it suggests that the clinical effect of white matter changes is likely a composite one where different clinical correlates interact to cause loss of independence.The presence of leukoaraiosis has been identified as a marker of less favorable prognosis also in the acute stroke settings. In particular, white matter changes have been associated with an increased risk of hemorrhagic transformation of the brain infarct in patients subjected to thrombolysis26; this increased risk is probably partially influenced by the copresence of lacunar infarcts.27 In this issue of Stroke, the article by Ay and colleagues28 adds further evidence about the prognostic significance of leukoaraiosis in this setting. These authors have shown that leukoaraiosis volume at the time of acute ischemic stroke is a predictor of infarct size growth. In this study, leukoaraiosis severity was volumetrically assessed whereas ischemic lesions on admission and follow-up were identified with diffusion and perfusion images. Clearly, this protocol is applicable only in centers with high expertise in neuroimaging techniques and not on a routine basis. But the relevance of the study is to have shown that a neuroimaging correlate of an underlying parenchyma and vessel disease is able to predict outcome in terms of infarct extension. When implemented in clinical practice, these data could provide a basis for a better selection of patients undergoing interventions in the acute phase of stroke.Taken together, these recently acquired data indicate that the view that white matter changes are an innocuous and incidental finding or a topic to be left to the discussion of a small group of researchers should be now disregarded. Like other biological markers of an underlying disease, leukoaraiosis needs to be carefully looked at, assessed, and quantified29; further studies will tell us whether this can be done by using simple visual rating scales or if it requires volume assessment and more sophisticated MRI techniques.The opinions in this editorial are not necessarily those of the editors or of the American Heart Association.DisclosuresNone.FootnotesCorrespondence to Leonardo Pantoni, MD, PhD, Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. E-mail [email protected] References 1 Hachinski VC, Potter P, Merskey H. Leuko-araiosis: an ancient term for a new problem. Can J Neurol Sci. 1986; 13 (4 Suppl): 533–534.CrossrefMedlineGoogle Scholar2 Hachinski VC, Potter P, Merskey H. Leuko-araiosis. Arch Neurol. 1987; 44: 21–23.CrossrefMedlineGoogle Scholar3 George AE, de Leon MJ, Gentes CI, Miller J, London E, Budzilovich GN, Ferris S, Chase N. Leukoencephalopathy in normal and pathologic aging: 1. CT of brain lucencies. AJNR Am J Neuroradiol. 1986; 7: 561–566.MedlineGoogle Scholar4 Pullicino P, Eskin T, Ketonen L. Prevalence of Binswanger's disease. Lancet. 1983; 1: 939.CrossrefMedlineGoogle Scholar5 Roman GC. Why not Binswanger's disease? Arch Neurol. 1988; 45: 141–143.CrossrefMedlineGoogle Scholar6 Johnson KA, Davis KR, Buonanno FS, Brady TJ, Rosen TJ, Growdon JH. Comparison of magnetic resonance and roentgen ray computed tomography in dementia. Arch Neurol. 1987; 44: 1075–1080.CrossrefMedlineGoogle Scholar7 George AE, de Leon MJ, Kalnin A, Rosner L, Goodgold A, Chase N. Leukoencephalopathy in normal and pathologic aging: 2. MRI of brain lucencies. AJNR Am J Neuroradiol. 1986; 7: 567–570.MedlineGoogle Scholar8 Fazekas F. Magnetic resonance signal abnormalities in asymptomatic individuals: their incidence and functional correlates. Eur Neurol. 1989; 29: 164–168.CrossrefMedlineGoogle Scholar9 Pantoni L, Garcia JH. The significance of cerebral white matter abnormalities 100 years after Binswanger's report. A review. Stroke. 1995; 26: 1293–1301.CrossrefMedlineGoogle Scholar10 Longstreth WT Jr, Manolio TA, Arnold A, Burke GL, Bryan N, Jungreis CA, Enright PL, O'Leary D, Fried L. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people: The Cardiovascular Health Study. Stroke. 1996; 27: 1274–1282.CrossrefMedlineGoogle Scholar11 de Leeuw FE, de Groot JC, Achten E, Oudkerk M, Ramos LM, Heijboer R, Hofman A, Jolles J, van Gijn J, Breteler MM. Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry. 2001; 70: 9–14.CrossrefMedlineGoogle Scholar12 Guttmann CR, Benson R, Warfield SK, Wei X, Anderson MC, Hall CB, Abu-Hasaballah K, Mugler JP III, Wolfson L. White matter abnormalities in mobility-impaired older persons. Neurology. 2000; 54: 1277–1283.CrossrefMedlineGoogle Scholar13 Teodorczuk A, O'Brien JT, Firbank MJ, Pantoni L, Poggesi A, Erkinjuntti T, Wallin A, Wahlund LO, Gouw A, Waldemar G, Schmidt R, Ferro JM, Chabriat H, Bazner H, Inzitari D; on behalf of the LADIS Group. White matter changes and late-life depressive symptoms: longitudinal study. Br J Psychiatry. 2007; 191: 212–217.CrossrefMedlineGoogle Scholar14 Hirono N, Kitagaki H, Kazui H, Hashimoto M, Mori E. Impact of white matter changes on clinical manifestation of Alzheimer's disease: a quantitative study. Stroke. 2000; 31: 2182–2188.CrossrefMedlineGoogle Scholar15 Pantoni L, Poggesi A, Inzitari D. The relation between white-matter lesions and cognition. Curr Opin Neurol. 2007; 20: 390–397.CrossrefMedlineGoogle Scholar16 Wen HM, Mok VC, Fan YH, Lam WW, Tang WK, Wong A, Huang RX, Wong KS. Effect of white matter changes on cognitive impairment in patients with lacunar infarcts. Stroke. 2004; 35: 1826–1830.LinkGoogle Scholar17 van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureira S, Pantoni L, Inzitari D, Erkinjuntti T, Crisby M, Waldemar G, Schmidt R, Fazekas F, Scheltens P. Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke. 2005; 36: 2116–2120.LinkGoogle Scholar18 van der Flier WM, van Straaten EC, Barkhof F, Ferro JM, Pantoni L, Basile AM, Inzitari D, Erkinjuntti T, Wahlund LO, Rostrup E, Schmidt R, Fazekas F, Scheltens P, for the LADIS study group. Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study. J Neurol Neurosurg Psychiatry. 2005; 76: 1497–1500.CrossrefMedlineGoogle Scholar19 Schmidt R, Petrovic K, Ropele S, Enzinger C, Fazekas F. Progression of leukoaraiosis and cognition. Stroke. 2007; 38: 2619–2625.LinkGoogle Scholar20 Schmidt R, Enzinger C, Ropele S, Schmidt H, Fazekas F, for the Austrian Stroke Prevention Study. Progression of cerebral white matter lesions: 6-year results of the Austrian Stroke Prevention Study. Lancet. 2003; 361: 2046–2048.CrossrefMedlineGoogle Scholar21 Sachdev P, Wen W, Chen X, Brodaty H. Progression of white matter hyperintensities in elderly individuals over 3 years. Neurology. 2007; 68: 214–222.CrossrefMedlineGoogle Scholar22 Inzitari D, Cadelo M, Marranci ML, Pracucci G, Pantoni L. Vascular deaths in elderly neurological patients with leukoaraiosis. J Neurol Neurosurg Psychiatry. 1997; 62: 177–181.CrossrefMedlineGoogle Scholar23 Briley DP, Haroon S, Sergent SM, Thomas S. Does leukoaraiosis predict morbidity and mortality? Neurology. 2000; 54: 90–94.CrossrefMedlineGoogle Scholar24 Prins ND, van Dijk EJ, den Heijer T, Vermeer SE, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM. Cerebral white matter lesions and the risk of dementia. Arch Neurol. 2004; 61: 1531–1534.CrossrefMedlineGoogle Scholar25 Inzitari D, Simoni M, Pracucci G, Poggesi A, Basile AM, Chabriat H, Erkinjuntti T, Fazekas F, Ferro JM, Hennerici M, Langhorne P, O'Brien J, Barkhof F, Visser MC, Wahlund LO, Waldemar G, Wallin A, Pantoni L, for the LADIS Study Group. Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study. Arch Intern Med. 2007; 167: 81–88.CrossrefMedlineGoogle Scholar26 Neumann-Haefelin T, Hoelig S, Berkefeld J, Fiehler J, Gass A, Humpich M, Kastrup A, Kucinski T, Lecei O, Liebeskind DS, Rother J, Rosso C, Samson Y, Saver JL, Yan B, for the MR Stroke Group. Leukoaraiosis is a risk factor for symptomatic intracerebral hemorrhage after thrombolysis for acute stroke. Stroke. 2006; 37: 2463–2466.LinkGoogle Scholar27 Palumbo V, Boulanger JM, Hill MD, Inzitari D, Buchan AM, for the CASES Investigators. Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke. Neurology. 2007; 68: 1020–1024.CrossrefMedlineGoogle Scholar28 Ay H, Arsava EM, Rosand J, Furie KL, Singhal AB, Schaefer PW, Wu O, Gonzalez RG, Koroshetz WJ, Sorensen AG. Severity of leukoaraiosis and susceptibility to infarct growth in acute stroke. Stroke. 2008; 39: 1409–1413.LinkGoogle Scholar29 Schmidt R, Scheltens P, Erkinjuntti T, Pantoni L, Markus HS, Wallin A, Barkhof F, Fazekas F, for the European Task Force on Age-Related White Matter Changes. White matter lesion progression. A surrogate endpoint for trials in cerebral small vessel disease. Neurology. 2004; 63: 139–144.CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited ByChoi J, Jin X, Kim H, Koh S, Cho H and Kim B (2022) High Mobility Group Box 1 as an Autocrine Chemoattractant for Oligodendrocyte Lineage Cells in White Matter Stroke, Stroke, 54:2, (575-586), Online publication date: 1-Feb-2023. Göthel-Ezzeiani A, Jansen O, Austein F, Hofmann A, Berg D, Meyne J and Hensler J (2022) Impact of leukoaraiosis or blood pressure on clinical outcome, mortality and symptomatic intracerebral hemorrhage after mechanical thrombectomy in acute ischemic stroke, Scientific Reports, 10.1038/s41598-022-25171-9, 12:1 Johnson L, Nemati S, Bonilha L, Rorden C, Busby N, Basilakos A, Newman-Norlund R, Hillis A, Hickok G and Fridriksson J (2022) Predictors beyond the lesion: Health and demographic factors associated with aphasia severity, Cortex, 10.1016/j.cortex.2022.06.013, 154, (375-389), Online publication date: 1-Sep-2022. Gulevskaya T, Anufriev P and Tanashyan М (2022) Morphology and pathogenesis of white matter changes in chronic cerebrovascular disease, Annals of Clinical and Experimental Neurology, 10.54101/ACEN.2022.2.9, 16:2, (78-88) Tang X, Jiang L, Luo Y, Fan H, Song L, Liu P and Chen Y (2021) Leukoaraiosis and acute ischemic stroke, European Journal of Neuroscience, 10.1111/ejn.15406, 54:6, (6202-6213), Online publication date: 1-Sep-2021. Chokesuwattanaskul A, Lertjitbanjong P, Thongprayoon C, Bathini T, Sharma K, Mao M, Cheungpasitporn W and Chokesuwattanaskul R (2020) Impact of obstructive sleep apnea on silent cerebral small vessel disease: a systematic review and meta-analysis, Sleep Medicine, 10.1016/j.sleep.2019.11.1262, 68, (80-88), Online publication date: 1-Apr-2020. Kim Y (2020) Subcortical Vascular Cognitive Impairment Stroke Revisited: Vascular Cognitive Impairment, 10.1007/978-981-10-1433-8_3, (25-33), . Wilmskoetter J, Marebwa B, Basilakos A, Fridriksson J, Rorden C, Stark B, Johnson L, Hickok G, Hillis A and Bonilha L (2019) Long-range fibre damage in small vessel brain disease affects aphasia severity, Brain, 10.1093/brain/awz251, 142:10, (3190-3201), Online publication date: 1-Oct-2019. Basilakos A, Stark B, Johnson L, Rorden C, Yourganov G, Bonilha L and Fridriksson J (2019) Leukoaraiosis Is Associated With a Decline in Language Abilities in Chronic Aphasia, Neurorehabilitation and Neural Repair, 10.1177/1545968319862561, 33:9, (718-729), Online publication date: 1-Sep-2019. Kim S, Yun J, Jeong S, Kim S, Yoo T, Lee J, Lim J, Jeong H, Nam K, Kwon H and Park J (2019) Kidney Dysfunction Impact on White Matter Hyperintensity Volume in Neurologically Healthy Adults, Scientific Reports, 10.1038/s41598-019-45109-y, 9:1 Zare A, Jahanshahi A, Rahnama'i M, Schipper S and van Koeveringe G (2018) The Role of the Periaqueductal Gray Matter in Lower Urinary Tract Function, Molecular Neurobiology, 10.1007/s12035-018-1131-8, 56:2, (920-934), Online publication date: 1-Feb-2019. Wei C, Zhang S, Liu J, Yuan R and Liu M (2018) Relationship of cardiac biomarkers with white matter hyperintensities in cardioembolic stroke due to atrial fibrillation and/or rheumatic heart disease, Medicine, 10.1097/MD.0000000000011892, 97:33, (e11892), Online publication date: 1-Aug-2018. Zasler N (2018) UBO Encyclopedia of Clinical Neuropsychology, 10.1007/978-3-319-57111-9_79, (3535-3536), . Wei C, Zhang S, Liu J, Lin J, Yang T, Zhang S and Liu M (2017) Association between Fibrinogen and Leukoaraiosis in Patients with Ischemic Stroke and Atrial Fibrillation, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2017.06.027, 26:11, (2630-2637), Online publication date: 1-Nov-2017. Fierini F, Poggesi A and Pantoni L (2017) Leukoaraiosis as an outcome predictor in the acute and subacute phases of stroke, Expert Review of Neurotherapeutics, 10.1080/14737175.2017.1371013, 17:10, (963-975), Online publication date: 3-Oct-2017. El-Gabalawy R, Patel R, Kilborn K, Blaney C, Hoban C, Ryner L, Funk D, Legaspi R, Fisher J, Duffin J, Mikulis D and Mutch W (2017) A Novel Stress-Diathesis Model to Predict Risk of Post-operative Delirium: Implications for Intra-operative Management, Frontiers in Aging Neuroscience, 10.3389/fnagi.2017.00274, 9 Saba L, Sanfilippo R, Balestrieri A, Zaccagna F, Argiolas G, Suri J and Montisci R (2017) Relationship between Carotid Computed Tomography Dual-Energy and Brain Leukoaraiosis, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2017.04.016, 26:8, (1824-1830), Online publication date: 1-Aug-2017. Mutch W and El-Gabalawy R (2017) Anesthesia and postoperative delirium: the agent is a strawman – the problem is CO2, Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 10.1007/s12630-017-0859-3, 64:6, (678-680), Online publication date: 1-Jun-2017. Feng L, Jiang H, Li Y, Teng F and He Y (2017) Effects of citicoline therapy on the network connectivity of the corpus callosum in patients with leukoaraiosis, Medicine, 10.1097/MD.0000000000005931, 96:4, (e5931), Online publication date: 1-Jan-2017. Zasler N (2017) UBO Encyclopedia of Clinical Neuropsychology, 10.1007/978-3-319-56782-2_79-2, (1-2), . David J, Ferrat E, Parisot J, Naga H, Lakroun S, Menasria F, Saddedine S, Natella P, Paillaud E, Fromentin I and Bastuji-Garin S (2016) White Matter Lesions: Prevalence and Clinical Phenotype in Asymptomatic Individuals Aged ≥50 Years, Dementia and Geriatric Cognitive Disorders, 10.1159/000448991, 42:3-4, (159-168), . Rodríguez García P and Rodríguez García D (2015) Diagnosis of vascular cognitive impairment and its main categories, Neurología (English Edition), 10.1016/j.nrleng.2011.12.013, 30:4, (223-239), Online publication date: 1-May-2015. Rodríguez García P and Rodríguez García D (2015) Diagnóstico del deterioro cognitivo vascular y sus principales categorías, Neurología, 10.1016/j.nrl.2011.12.014, 30:4, (223-239), Online publication date: 1-May-2015. Saba L, Raz E, Bassareo P, di Martino M, de Cecco C, Mercuro G, Grassi R, Suri J and Piga M (2015) Is There an Association between Cerebral Microbleeds and Leukoaraiosis?, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2014.07.035, 24:2, (284-289), Online publication date: 1-Feb-2015. Conklin J, Silver F, Mikulis D and Mandell D (2014) Are acute infarcts the cause of leukoaraiosis? Brain mapping for 16 consecutive weeks, Annals of Neurology, 10.1002/ana.24285, 76:6, (899-904), Online publication date: 1-Dec-2014. Salat D (2014) Imaging small vessel-associated white matter changes in aging, Neuroscience, 10.1016/j.neuroscience.2013.11.041, 276, (174-186), Online publication date: 1-Sep-2014. Goldstein M and Mascitelli L (2014) Regarding long-term statin therapy: Are we trading stronger hearts for weaker brains?, Medical Hypotheses, 10.1016/j.mehy.2014.06.010, 83:3, (346-351), Online publication date: 1-Sep-2014. Huang Y, Xia Z, Wei W, Gao G, Gong J, Li Y and Zhang W (2014) The impact of leucoaraiosis on neurological function recovery in elderly patients with acute cerebral infarction: Clinical study involving 279 Chinese patients, Journal of International Medical Research, 10.1177/0300060513507386, 42:3, (857-862), Online publication date: 1-Jun-2014. Poggesi A, Pantoni L and Inzitari D (2014) Consequences of cerebral small vessel disease: disability, mortality, and prognosis Cerebral Small Vessel Disease, 10.1017/CBO9781139382694.023, (273-282) (2014) Clinical aspects of cerebral small vessel disease Cerebral Small Vessel Disease, 10.1017/CBO9781139382694.019, (217-310) Yadav B, Oh S, Kim N and Shin B (2014) Association of rs2075575 and rs9951307 Polymorphisms of AQP-4 Gene with Leukoaraiosis, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2013.10.017, 23:5, (1199-1206), Online publication date: 1-May-2014. Rincon F and Wright C (2014) Current pathophysiological concepts in cerebral small vessel disease, Frontiers in Aging Neuroscience, 10.3389/fnagi.2014.00024, 6 Calabrò R, Spadaro L and Bramanti P (2014) Cerebrovascular Diseases: Post-stroke Depression and Anhedonia Anhedonia: A Comprehensive Handbook Volume II, 10.1007/978-94-017-8610-2_15, (301-318), . Ogbole G, Owolabi M and Yusuf B (2013) White Matter Changes on Magnetic Resonance Imaging: A Risk Factor for Stroke in an African Population?, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2013.01.003, 22:7, (e227-e233), Online publication date: 1-Oct-2013. (2013) Vascular cognitive impairment The Behavioral and Cognitive Neurology of Stroke, 10.1017/CBO9781139058988.002, (1-31) Freund W, Faust S, Birklein F, Gaser C, Wunderlich A, Müller M, Billich C, Juchems M, Schmitz B, Grön G and Schütz U (2012) Substantial and reversible brain gray matter reduction but no acute brain lesions in ultramarathon runners: experience from the TransEurope-FootRace Project, BMC Medicine, 10.1186/1741-7015-10-170, 10:1, Online publication date: 1-Dec-2012. Mohd Taib N, Abdullah W, Shuaib I, Magosso E and Isa S (2012) Diffusion tensor imaging and tractography for the assessment of leukoaraiosis 2012 IEEE EMBS Conference on Biomedical Engineering and Sciences (IECBES 2012), 10.1109/IECBES.2012.6498055, 978-1-4673-1666-8, (857-860) Neal J (2011) Vascular dementia: why pathology is still important, Reviews in Clinical Gerontology, 10.1017/S0959259811000207, 22:1, (35-51), Online publication date: 1-Feb-2012. Calabrò R, Gervasi G and Bramanti P (2011) Does l-arginine supplementation play a role in cerebral small vessels disease? Implication in the treatment of leukoaraiosis, Medical Hypotheses, 10.1016/j.mehy.2011.07.012, 77:4, (671-673), Online publication date: 1-Oct-2011. Reig-Puig L, Antón-Rodrigo I and Sánchez-Ferrín P (2011) Relación entre hipertensión arterial y la demencia, Hipertensión y Riesgo Vascular, 10.1016/j.hipert.2011.08.002, 28:5-6, (182-195), Online publication date: 1-Sep-2011. Maki T, Ihara M, Fujita Y, Nambu T, Miyashita K, Yamada M, Washida K, Nishio K, Ito H, Harada H, Yokoi H, Arai H, Itoh H, Nakao K, Takahashi R and Tomimoto H (2011) Angiogenic and Vasoprotective Effects of Adrenomedullin on Prevention of Cognitive Decline After Chronic Cerebral Hypoperfusion in Mice, Stroke, 42:4, (1122-1128), Online publication date: 1-Apr-2011. Zasler N (2011) UBO Encyclopedia of Clinical Neuropsychology, 10.1007/978-0-387-79948-3_79, (2571-2571), . Huang Y, Zhang W, Lin L, Feng J, Chen F, Wei W, Zhao X, Guo W, Li J, Yin W and Li L (2010) Is endothelial dysfunction of cerebral small vessel responsible for white matter lesions after chronic cerebral hypoperfusion in rats?, Journal of the Neurological Sciences, 10.1016/j.jns.2010.08.035, 299:1-2, (72-80), Online publication date: 1-Dec-2010. Chung C and Hu H (2010) Pathogenesis of leukoaraiosis: Role of jugular venous reflux, Medical Hypotheses, 10.1016/j.mehy.2010.01.042, 75:1, (85-90), Online publication date: 1-Jul-2010. Pantoni L (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges, The Lancet Neurology, 10.1016/S1474-4422(10)70104-6, 9:7, (689-701), Online publication date: 1-Jul-2010. Huang Y, Zhang W, Lin L, Feng J, Zhao X, Guo W and Wei W (2010) Could changes in arterioles impede the perivascular drainage of interstitial fluid from the cerebral white matter in leukoaraiosis?, Neuropathology and Applied Neurobiology, 10.1111/j.1365-2990.2009.01049.x, 36:3, (237-247), Online publication date: 1-Apr-2010. Kuchel G, Moscufo N, Guttmann C, Zeevi N, Wakefield D, Schmidt J, DuBeau C and Wolfson L (2009) Localization of Brain White Matter Hyperintensities and Urinary Incontinence in Community-Dwelling Older Adults, The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 10.1093/gerona/glp037, 64A:8, (902-909), Online publication date: 1-Aug-2009. Pu Y, Liu L, Zou X, Chen P, Wang Y, Zhou Y, Dong K, Zhao X, Wang C and Wang Y (2013) Relationship between leukoaraiosis and cerebral large artery stenosis, Neurological Research, 10.1179/174313209X444071, 31:4, (376-380), Online publication date: 1-May-2009. Henskens L, van Oostenbrugge R, Kroon A, Hofman P, Lodder J and de Leeuw P (2009) Detection of silent cerebrovascular disease refines risk stratification of hypertensive patients, Journal of Hypertension, 10.1097/HJH.0b013e3283232c96, 27:4, (846-853), Online publication date: 1-Apr-2009. Hachinski V (2008) World Stroke Day 2008, Stroke, 39:9, (2407-2408), Online publication date: 1-Sep-2008. May 2008Vol 39, Issue 5 Advertisement Article InformationMetrics https://doi.org/10.1161/STROKEAHA.107.505602PMID: 18340098 Originally publishedMarch 13, 2008 Keywordsprognosiswhite matter changesstrokedisabilityMRIleukoaraiosisPDF download Advertisement
Referência(s)