Mecanismos y consecuencias clínicas | 08 JUL 19

Enfermedad cerebral de pequeños vasos

Numerosas personas son asintomáticas, pero cuando el número y el tipo de lesiones aumenta, se asocian con deterioro cognitivo, demencia, depresión, problemas de movilidad y aumento del riesgo de accidente cerebrovascular
Autor: Wardlaw JM, Smith C, Dichgans M  Lancet Neurol 2019 Vol18, Issue 7
INDICE:  1. Página 1 | 2. Referencias bibliográficas
Referencias bibliográficas

1 Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013; 12: 483–97.

2 Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration: a united approach. Lancet Neurol 2013;12: 822–38.

3 van Veluw SJ, Shih AY, Smith EE, et al. Detection, risk factors, and functional consequences of cerebral microinfarcts. Lancet Neurol 2017; 16: 730–40.

4 Debette S, Schilling S, Duperron MG, Larsson SC, Markus HS. Clinical significance of magnetic resonance imaging markers of vascular brain injury: a systematic review and meta-analysis. JAMA Neurol 2019; 76: 81–94.

5 Georgakis MK, Duering M, Wardlaw JM, Dichgans M. WMH and long-term outcomes in ischemic stroke: a systematic review and meta-analysis. Neurology 2019; 92: e1298–308.

6 Kapasi A, DeCarli C, Schneider JA. Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathol 2017; 134: 171–86.

7 Bos D, Wolters FJ, Darweesh SKL, et al. Cerebral small vessel disease and the risk of dementia: a systematic review and meta-analysis of population-based evidence. Alzheimers Dement 2018; 14: 1482–92.

8 Munoz Maniega S, Chappell FM, Valdes Hernandez MC, et al. Integrity of normal-appearing white matter: influence of age, visible lesion burden and hypertension in patients with small-vessel disease. J Cereb Blood Flow Metab 2017; 37: 644–56.

9 Baykara E, Gesierich B, Adam R, et al. A novel imaging marker for small vessel disease based on skeletonization of white matter tracts and diffusion histograms. Ann Neurol 2016;80: 581–92.

10 Duering M, Righart R, Wollenweber FA, Zietemann V, Gesierich B, Dichgans M. Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts. Neurology 2015;84: 1685–92.

11 Duering M, Finsterwalder S, Baykara E, et al. Free water determines diffusion alterations and clinical status in cerebral small vessel disease. Alzheimers Dement 2018; 14: 764–74.

12 Vinters HV, Zarow C, Borys E, et al. Review: Vascular dementia: clinicopathologic and genetic considerations. Neuropathol Appl Neurobiol 2018; 44: 247–66.

13 Arvanitakis Z, Capuano AW, Leurgans SE, Buchman AS, Bennett DA, Schneider JA. The relationship of cerebral vessel pathology to brain microinfarcts. Brain Pathology 2017; 27: 77–85.

14 Skrobot OA, Attems J, Esiri M, et al. Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment. Brain 2016;139: 2957–69.

15 Iadecola C. The neurovascular unit coming of age: A journey through neurovascular coupling in health and disease. Neuron 2017;96: 17–42.

16 Rajani RM, Quick S, Ruigrok SR, et al. Reversal of endothelial dysfunction reduces white matter vulnerability in cerebral small vessel disease in rats. Sci Transl Med 2018; 10: eaam9507.

17 Bugiani M, Kevelam SH, Bakels HS, et al. Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL). Neurology 2016; 87: 1777–86.

18 Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol 2018; 17: 1016–24.

19 Petersen MA, Ryu JK, Akassoglou K. Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics. Nat Rev Neurosci 2018; 19: 283.

20 Malik R, Chauhan G, Traylor M, et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet 2018; 50: 524–37.

21 Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N. Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Ann Neurol 2015; 78: 887–900.

22 Nation DA, Sweeney MD, Montagne A, et al. Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat Med 2019; 25: 270–76.

23 Wardlaw JM, Doubal FN, Valdes-Hernandez MC, et al. Blood-brain barrier permeability and long term clinical and imaging outcomes in cerebral small vessel disease. Stroke 2013; 44: 525–27.

24 Li Y, Li M, Zuo L, et al. Compromised blood-brain barrier integrity is associated with total magnetic resonance imaging burden of cerebral small vessel disease. Front Neurol 2018; 9: 221.

25 Huisa BN, Caprihan A, Thompson J, Prestopnik J, Qualls CR, Rosenberg GA. Long-term blood-brain barrier permeability changes in Binswanger disease. Stroke 2015; 46: 2413–18.

26 Raja R, Rosenberg GA, Caprihan A. MRI measurements of blood-brain barrier function in dementia: a review of recent studies. Neuropharmacology 2018; 134: 259–71.

27 Zhang CE, Wong SM, Uiterwijk R, et al. Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging. Brain Imaging Behav 2018;published online March 23. DOI:10.1007/s11682-018-9855-7.

28 Wardlaw JM, Makin SJ, Valdés Hernández MC, et al. Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study. Alzheimers Dement 2017; 13: 634–43.

29 Rost NS, Cougo P, Lorenzano S, et al. Diffuse microvascular dysfunction and loss of white matter integrity predict poor outcomes in patients with acute ischemic stroke. J Cereb Blood Flow Metab 2018; 38: 75–86.

30 Promjunyakul NO, Dodge HH, Lahna D, et al. Baseline NAWM structural integrity and CBF predict periventricular WMH expansion over time. Neurology 2018; 90: e2119–26.

31 van Leijsen EMC, Bergkamp MI, van Uden IWM, et al. Progression of white matter hyperintensities preceded by heterogeneous decline of microstructural integrity. Stroke 2018; 49: 1386–93.

32 Duering M, Csanadi E, Gesierich B, et al. Incident lacunes preferentially localize to the edge of white matter hyperintensities: insights into the pathophysiology of cerebral small vessel disease. Brain 2013; 136: 2717–26.

33 Hainsworth AH, Oommen AT, Bridges LR. Endothelial cells and human cerebral small vessel disease. Brain Pathol 2015; 25: 44–50.

34 De Guio F, Mangin JF, Duering M, Ropele S, Chabriat H, Jouvent E. White matter edema at the early stage of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 2015; 46: 258–61.

35 Wardlaw JM, Chappell FM, Valdes Hernandez MDC, et al. White matter hyperintensity reduction and outcomes after minor stroke. Neurology 2017; 89: 1003–10.

36 Shi Y, Thrippleton MJ, Makin SD, et al. Cerebral blood flow in small vessel disease: a systematic review and meta-analysis. J Cereb Blood Flow Metab 2016; 36: 1653–67.

37 Kisler K, Nelson AR, Montagne A, Zlokovic BV. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci 2017; 18: 419–34.

38 Nylander R, Fahlstrom M, Rostrup E, et al. Quantitative and qualitative MRI evaluation of cerebral small vessel disease in an elderly population: a longitudinal study. Acta Radiol 2017;59: 612–18.

39 Ostergaard L, Sondergaard T, Moreton F, et al. Cerebral small vessel disease: capillary pathways to stroke and cognitive decline. J Cereb Blood Flow Metab 2016; 36: 302–25.

40 Thrippleton MJ, Shi Y, Blair G, et al. Cerebrovascular reactivity measurement in cerebral small vessel disease: rationale and reproducibility of a protocol for MRI acquisition and image processing. Int J Stroke 2018; 13: 195–206.

41 Huneau C, Houot M, Joutel A, et al. Altered dynamics of neurovascular coupling in CADASIL. Ann Clin Transl Neurol 2018;5: 788–802.

42 Blair G, Doubal FN, Thrippleton MJ, Marshall I, Wardlaw JM. Magnetic resonance imaging for assessment of cerebrovascular reactivity in cerebral small vessel disease. A systematic review. J Cereb Blood Flow Metab 2016; 36: 833–41.

43 Sam K, Crawley AP, Conklin J, et al. Development of white matter hyperintensity is preceded by reduced cerebrovascular reactivity. Ann Neurol 2016; 80: 277–85.

44 Blair, G. Thrippleton, MJ, Shi, Y, et al. Intracranial functional haemodynamic relationships in patients with cerebral small vessel disease. bioRxiv 2019; 572818.

45 Shi Y, Thrippleton MJ, Blair GW, et al. Small vessel disease is associated with altered cerebrovascular pulsatility but not resting cerebral blood flow J Cereb Blood Flow Metab 2018; published online Oct 8. DOI:10.1177/0271678X18803956.

46 Brown R, Benveniste H, Black SE, et al. Understanding the role of the perivascular space in cerebral small vessel disease. Cardiovasc Res 2018; 114: 1462–73.

47 Bouvy WH, Biessels GJ, Kuijf HJ, Kappelle LJ, Luijten PR, Zwanenburg JJ. Visualization of perivascular spaces and perforating arteries with 7 T magnetic resonance imaging. Invest Radiol 2014;49: 307–13.

48 Riba-Llena I, Jimenez-Balado J, Castane X, et al. Arterial stiffness is associated with basal ganglia enlarged perivascular spaces and cerebral small vessel disease load. Stroke 2018; 49: 1279–81.

49 Duperron MG, Tzourio C, Sargurupremraj M, et al. Burden of dilated perivascular spaces, an emerging marker of cerebral small vessel disease, is highly heritable. Stroke 2018; 49: 282–87.

50 Aribisala BS, Wiseman S, Morris Z, et al. Circulating inflammatory markers are associated with MR visible perivascular spaces but not directly with white matter hyperintensities. Stroke 2014; 45: 605–07.

51 Loos CM, Klarenbeek P, van Oostenbrugge RJ, Staals J. Association between perivascular spaces and progression of white matter hyperintensities in lacunar stroke patients. PLoS One 2015;10: e0137323.

52 Lau KK, Pego P, Mazzucco S, et al. Age and sex-specific associations of carotid pulsatility with small vessel disease burden in transient ischemic attack and ischemic stroke. Int J Stroke 2018;13: 832–39.

53 Shi Y, Thrippleton MJ, Marshall I, Wardlaw JM. Intracranial pulsatility in patients with cerebral small vessel disease:a systematic review. Clin Sci (Lond) 2018; 132: 157–71.

54 Mestre H, Tithof J, Du T, et al. Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension. Nat Commun 2018; 9: 4878.

55 Loos CMJ, Makin SDJ, Staals J, Dennis MS, van Oostenbrugge RJ, Wardlaw JM. Long-term morphological changes of symptomatic lacunar infarcts and surrounding white matter on structural magnetic resonance imaging. Stroke 2018; 49: 1183–88.

56 Dickie DA, Karama S, Ritchie SJ, et al. Progression of white matter disease and cortical thinning are not related in older community-dwelling subjects. Stroke 2016; 47: 410–16.

57 Schmidt R, Seiler S, Loitfelder M. Longitudinal change of small-vessel disease-related brain abnormalities. J Cereb Blood Flow Metab 2016; 36: 26–39.

58 van Leijsen EMC, van Uden IWM, Ghafoorian M, et al. Nonlinear temporal dynamics of cerebral small vessel disease: the RUN DMC study. Neurology 2017; 89: 1569–77.

59 Hinman JD, Lee MD, Tung S, Vinters HV, Carmichael ST. Molecular disorganization of axons adjacent to human lacunar infarcts. Brain 2015; 138: 736–45.

60 Ter Telgte A, van Leijsen EMC, Wiegertjes K, Klijn CJM, Tuladhar AM, de Leeuw FE. Cerebral small vessel disease: from a focal to a global perspective. Nat Rev Neurol 2018; 14: 387–98.

61 Banerjee G, Jang H, Kim HJ, et al. Total MRI small vessel disease burden correlates with cognitive performance, cortical atrophy, and network measures in a memory clinic population. J Alzheimers Dis 2018; 63: 1485–97.

62 Staals J, Makin SDJ, Doubal F, Dennis M, Wardlaw JM. Stroke subtype, vascular risk factors and total MRI brain small vessel disease burden. Neurology 2014; 83: 1228–34.

63 Pinter D, Ritchie SJ, Doubal F, et al. Impact of small vessel disease in the brain on gait and balance. Sci Rep 2017; 7: 41637.

64 Paradise MB, Shepherd CE, Wen W, Sachdev PS. Neuroimaging and neuropathology indices of cerebrovascular disease burden: a systematic review. Neurology 2018; 91: 310–20.

65 Rensma SP, van Sloten TT, Launer LJ, Stehouwer CDA. Cerebral small vessel disease and risk of incident stroke, dementia and depression, and all-cause mortality: a systematic review and meta-analysis. Neurosci Biobehav Rev 2018; 90: 164–73.

66 Kim YJ, Kwon HK, Lee JM, et al. Gray and white matter changes linking cerebral small vessel disease to gait disturbances. Neurology 2016; 86: 1199–207.

67 Hollocks MJ, Lawrence AJ, Brookes RL, et al. Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes. Brain 2015;138: 3803–15.

68 van Agtmaal MJM, Houben A, Pouwer F, Stehouwer CDA, Schram MT. Association of microvascular dysfunction with late-life depression: a systematic review and meta-analysis. JAMA Psychiatry 2017; 74: 729–39.

69 van der Holst HM, van Uden IW, Tuladhar AM, et al. Cerebral small vessel disease and incident parkinsonism: the RUN DMC study. Neurology 2015; 85: 1569–77.

70 Valdes Hernandez MC, Maconick LC, Munoz Maniega S, et al. A comparison of location of acute symptomatic versus ‘silent’ small vessel lesions. Int J Stroke 2015; 10: 1044–50.

71 Duering M, Gesierich B, Seiler S, et al. Strategic white matter tracts for processing speed deficits in age-related small vessel disease. Neurology 2014; 82: 1946–50.

72 Backhouse EV, McHutchison CA, Cvoro V, Shenkin SD, Wardlaw JM. Early life risk factors for cerebrovascular disease: a systematic review and meta-analysis. Neurology 2017; 88: 976–84.

73 Jokinen H, Melkas S, Madureira S, et al. Cognitive reserve moderates long-term cognitive and functional outcome in cerebral small vessel disease. J Neurol Neurosurg Psychiatry 2016;87: 1296–302.

74 Ling Y, De Guio F, Duering M, et al. Predictors and clinical impact of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 2017;48: 283–89.

75 Heinen R, Vlegels N, de Bresser J, Leemans A, Biessels GJ, Reijmer YD. The cumulative effect of small vessel disease lesions is reflected in structural brain networks of memory clinic patients. Neuroimage Clin 2018; 19: 963–69.

76 van den Berg E, Geerlings MI, Biessels GJ, Nederkoorn PJ, Kloppenborg RP. White matter hyperintensities and cognition in mild cognitive impairment and Alzheimer’s disease: a domain-specific meta-analysis. J Alzheimers Dis 2018; 63: 515–27.

77 Quinn TJ, McCleery J. Diagnosis in vascular dementia, applying ‘Cochrane diagnosis rules’ to ‘dementia diagnostic tools’. Clin Sci (Lond) 2017; 131: 729–32.

78 Peres R, De Guio F, Chabriat H, Jouvent E. Alterations of the cerebral cortex in sporadic small vessel disease: a systematic review of in vivo MRI data. J Cereb Blood Flow Metab 2016;36: 681–95.

79 Chabriat H, Hervé D, Duering M, et al. Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: prospective cohort study. Stroke 2016; 47: 4–11.

80 Rizvi B, Narkhede A, Last BS, et al. The effect of white matter hyperintensities on cognition is mediated by cortical atrophy. Neurobiol Aging 2018; 64: 25–32.

81 Makin SD, Doubal FN, Shuler K, et al. The impact of early-life intelligence quotient on post stroke cognitive impairment. Eur Stroke J 2018; 3: 145–56.

82 Zieren N, Duering M, Peters N, et al. Education modifies the relation of vascular pathology to cognitive function: cognitive reserve in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Neurobiol Aging 2013;34: 400–07.

83 Elbaz A, Vicente-Vytopilova P, Tavernier B, et al. Motor function in the elderly: evidence for the reserve hypothesis. Neurology 2013;81: 417–26.

84 Bath PM, Wardlaw JM. Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions. Int J Stroke 2015; 10: 469–78.

85 Kwok CS, Shoamanesh A, Copley HC, Myint PK, Loke YK, Benavente OR. Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials. Stroke 2015; 46: 1014–23.

86 Pearce LA, McClure LA, Anderson DC, et al. Effects of long-term blood pressure lowering and dual antiplatelet treatment on cognitive function in patients with recent lacunar stroke: a secondary analysis from the SPS3 randomised trial. Lancet Neurol 2014; 13: 1177–85.

87 van Middelaar T, Argillander TE, Schreuder F, Deinum J, Richard E, Klijn CJM. Effect of antihypertensive medication on cerebral small vessel disease: a systematic review and meta-analysis. Stroke 2018;49: 1531–33.

88 Croall ID, Tozer DJ, Moynihan B, et al. Effect of standard vs intensive blood pressure control on cerebral blood flow in small vessel disease: the PRESERVE randomized clinical trial. JAMA Neurol 2018; 75: 720–27.

89 Xiong Y, Wong A, Cavalieri M, et al. Prestroke statins, progression of white matter hyperintensities, and cognitive decline in stroke patients with confluent white matter hyperintensities. Neurotherapeutics 2014; 11: 606–11.

90 Ji T, Zhao Y, Wang J, et al. Effect of Low-dose statins and apolipoprotein E genotype on cerebral small vessel disease in older hypertensive patients: a subgroup analysis of a randomized clinical trial. J Am Med Dir Assoc 2018; 19: 995–1002.

91 The ENOS Trial Investigators. Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial. Lancet 2015; 385: 617–28.

92 Blair GW, Appleton JP, Flaherty K, et al. Tolerability, safety and intermediary pharmacological effects of cilostazol and isosorbide mononitrate, alone and combined, in patients with lacunar ischaemic stroke: the LACunar Intervention-1 (LACI-1) trial, a randomised clinical trial. EClinicalMedicine 2019; published online April 23, DOI:10.1016/j.eclinm.2019.04.001

93 Blair GW, Appleton JP, Law ZK, et al. Preventing cognitive decline and dementia from cerebral small vessel disease: the LACI-1 Trial. Protocol and statistical analysis plan of a phase IIa dose escalation trial testing tolerability, safety and effect on intermediary endpoints of isosorbide mononitrate and cilostazol, separately and in combination. Int J Stroke 2018; 13: 530–38.

94 Tai SY, Chien CY, Chang YH, Yang YH. Cilostazol use is associated with reduced risk of dementia: a nationwide cohort study. Neurotherapeutics 2017; 14: 784–91.

95 Hankey GJ. The role of nutrition in the risk and burden of stroke: an update of the evidence. Stroke 2017; 48: 3168–74.

96 Karama S, Ducharme S, Corley J, et al. Cigarette smoking and thinning of the brain’s cortex. Mol Psychiatry 2015; 20: 778–85.

97 Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet 2015;385: 2255–63.

98 Sabayan B, van Vliet P, de Ruijter W, Gussekloo J, de Craen AJ, Westendorp RG. High blood pressure, physical and cognitive function, and risk of stroke in the oldest old: the Leiden 85-Plus Study. Stroke 2013; 44: 15–20.

99 Pettersen JA, Keith J, Gao F, Spence JD, Black SE. CADASIL accelerated by acute hypotension: arterial and venous contribution to leukoaraiosis. Neurology 2017; 88: 1077–80.

100 Ji T, Zhao Y, Wang J, et al. Effect of low-dose statins and apolipoprotein E genotype on cerebral small vessel disease in older hypertensive patients: a subgroup analysis of a randomized clinical trial. J Am Med Dir Assoc 2018; 19: 995–1002.

101 Bath PM, Scutt P, Blackburn DJ, et al. Intensive versus guideline blood pressure and lipid lowering in patients with previous stroke: main results from the pilot ‘Prevention of Decline in Cognition after Stroke Trial’ (PODCAST) randomised controlled trial. PLoS One 2017; 12: e0164608.

102 Humphreys CA, Jansen MA, Munoz-Maniega S, et al. A protocol for precise comparisons of small vessel disease lesions between ex vivo MRI and histopathology. Int J Stroke 2019; 14: 310–20.



Usted debe ingresar al sitio con su cuenta de usuario IntraMed para ver los comentarios de sus colegas o para expresar su opinión. Si ya tiene una cuenta IntraMed o desea registrase, ingrese aquí