Review article

Advances in study on risk factors related to cerebral microbleeds and on treatment decision-making when cerebral microbleeds merging related diseases

  • ZHAO Lijuan ,
  • CHENG Tao ,
  • SHUI Xinjun ,
  • YUE Dongqi ,
  • QIN Shaochen ,
  • LIU Xiaoling ,
  • WANG Jiali ,
  • FU Yi
Expand
  • 1. Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
    2a. Department of Neurology, 2b. Department of Neurosurgery, Shanxi Cardiovascular Hospital,Taiyuan 030024, China
    3. Department of Neurology, The Hospital Affiliated to Shanxi University of Chinese Medicine,Taiyuan 030024, China
    4. Department of Neurology, Yuncheng Central Hospital of Shanxi Province,Yuncheng 044000, China

Received date: 2024-03-10

  Accepted date: 2024-06-13

  Online published: 2024-08-25

Abstract

Cerebral microbleeds, belongs to the category of cerebral small blood vessel disease, is a vascular lesion of subcortical or deep brain tissue caused by a variety of risk factors. In recent years, with the development of imaging and the wide use of antithrombotic drugs, the detection rate of cerebral microbleeds has gradually increased. Although mostly regarded as asymptomatic, cerebral microbleeds may increase the risk of cognitive dysfunction, hemorrhagic transformation after cerebral infarction, cerebral hemorrhage, etc. It is of great significance to summarize the progress of the epidemiology and related risk factors of cerebral microbleeds. Risk factors for cerebral microbleeds include genetic factors (ApoE ε4 gene (OR=2.54), NOTCH3 mutation, homozygous mutation in HTRA 1 gene, Fabry disease), advanced age and male (P=0.043), smoking (OR=5.791) and alcohol consumption (OR=7.306), hypertension (OR=1. 049), diabetes (P=0.005), dyslipidemia (P<0.05), cerebral amyloid angiopathy (OR=2.210), hyperhomocysteemia (P<0.05), hyperuricemia (OR:1. 98), renal dysfunction and dialysis (P=0.0041), critical illness (60% of patients had cerebral microhemorrhage after ECMO). Other rare risk factors include cardiac surgery, infective endocarditis, reversible posterior encephalopathy syndrome, moyamoya disease, obstructive sleep apnea syndrome, craniocerebral radiotherapy, and traumatic brain injury can all lead to the occurrence of cerebral microbleeds. At present, age, hypertension and ApoE gene polymorphism are specific risk factors for cerebral microhemorrhage. Whether other risk factors has not reached the overwhelming consensus. Cerebral microbleeds does not require treatment, but in clinical practice, patients with cerebral infarction or atrial fibrillation combined with cerebral microbleeds should be carefully considered. For patients with ischemic stroke/TIA complicated with cerebral microbleeds, antiplatelet therapy is still beneficial, and cerebral microbleeds should not be a contraindication to intravenous thrombolysis (intravenous thrombolysis, IVT) or endovascular treatment (endovascular therapy, EVT). However, for patients with high-load (>10) cerebral microbleeds, even with the IVT/EVT treatment indications, the pros and cons should also be weighed according to the patient's specific situation. For patients with atrial fibrillation complicated with cerebral microbleeds, when the number of cerebral microbleeds is larger or lesions located in the cortical areas, and the risk of cerebral microbleeds is higher, safer new anticoagulants are recommended. At present, there is no consensus between the domestic and foreign medical circles on the risk factors of cerebral microbleeds and the treatment plan and individualized intervention of ischemic stroke combined with cerebral microbleeds, and large-scale clinical studies are still needed for further exploration.

Cite this article

ZHAO Lijuan , CHENG Tao , SHUI Xinjun , YUE Dongqi , QIN Shaochen , LIU Xiaoling , WANG Jiali , FU Yi . Advances in study on risk factors related to cerebral microbleeds and on treatment decision-making when cerebral microbleeds merging related diseases[J]. Journal of Diagnostics Concepts & Practice, 2024 , 23(04) : 430 -438 . DOI: 10.16150/j.1671-2870.2024.04.012

References

[1] GOOS J D, VAN DER FLIER W M, KNOL D L, et al. Clinical relevance of improved microbleed detection by susceptibility-weighted magnetic resonance imaging[J]. Stroke, 2011, 42(7):1894-1900.
[2] HAN F, ZHAI F F, WANG Q, et al. Prevalence and risk factors of cerebral small vessel disease in a Chinese population-based sample[J]. J Stroke, 2018, 20(2):239-246.
[3] POELS M M, VERNOOIJ M W, IKRAM M A, et al. Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study[J]. Stroke, 2010, 41(10 Suppl):S103-S106.
[4] GORMLEY K, BEVAN S, MARKUS H S. Polymorphisms in genes of the renin-angiotensin system and cerebral small vessel disease[J]. Cerebrovasc Dis, 2007, 23(2-3):148-155.
[5] 倪民桦, 颜林枫, 崔光彬. 定量磁化率图在脑微出血中的研究进展[J]. 国际医学放射学杂志, 2022, 45(3):303-306.
  NI M H, YAN L F, CUI G B. The progress of quantitative susceptibility mapping in the diagnosis of cerebral microbleeds[J]. Int J Med Radiol, 2022, 45(3):303-306.
[6] GREENBERG S M, VERNOOIJ M W, CORDONNIER C, et al. Cerebral microbleeds: a guide to detection and interpretation[J]. Lancet Neurol, 2009, 8(2):165-174.
[7] GREGOIRE S M, CHAUDHARY U J, BROWN M M, et al. The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds[J]. Neurology, 2009, 73(21):1759-1766.
[8] CORDONNIER C, POTTER G M, JACKSON C A, et al. Improving interrater agreement about brain microbleeds: development of the Brain Observer MicroBleed Scale (BOMBS)[J]. Stroke, 2009, 40(1):94-99.
[9] 徐大飞, 楚兰. 缺血性脑卒中患者合并脑微出血的危险因素分析[J]. 中国神经免疫学和神经病学杂志, 2020, 27(2):143-146.
  XU D F, CHU L. The studies of risk factors of cerebral ischemic stroke complicated with cerebral microbleeds[J]. Chin J Neuroimmunol Neurol, 2020, 27(2):143-146.
[10] MAXWELL S S, JACKSON C A, PATERNOSTER L, et al. Genetic associations with brain microbleeds: Systema-tic review and meta-analyses[J]. Neurology, 2011, 77(2):158-167.
[11] INGALA S, MAZZAI L, SUDRE C H, et al. The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals[J]. Neurobiol Aging, 2020, 95:104-114.
[12] LI H Q, CAI W J, HOU X H, et al. Genome-Wide Association Study of Ce-rebral Microbleeds on MRI[J]. Neurotox Res, 2020, 37(1):146-155.
[13] GRAFF-RADFORD J, LESNICK T, RABINSTEIN A A, et al. Cerebral microbleed incidence, relationship to amyloid burden: The Mayo Clinic Study of Aging[J]. Neuro-logy, 2020, 94(2):e190-e199.
[14] JOUTEL A, CORPECHOT C, DUCROS A, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia[J]. Nature, 1996, 383(6602):707-710.
[15] ARVANITAKIS Z, LEURGANS S E, WANG Z, et al. Cerebral amyloid angiopathy pathology and cognitive domains in older persons[J]. Ann Neurol, 2011, 69(2):320-327.
[16] LEE J S, KANG C H, PARK S Q, et al. Clinical significance of cerebral microbleeds locations in CADASIL with R544C NOTCH3 mutation[J]. PLoS One, 2015, 10(2):e0118163.
[17] VAN DEN BOOM R, LESNIK OBERSTEIN S A, FERRARI M D, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: MR imaging findings at different ages- -3rd-6th decades[J]. Radiology, 2003, 229(3):683-690.
[18] DICHGANS M, HOLTMANNSP?TTER M, HERZOG J, et al. Cerebral microbleeds in CADASIL: a gradient-echo magnetic resonance imaging and autopsy study[J]. Stroke, 2002, 33(1):67-71.
[19] 何志义. 应重视伴皮质下梗死和白质脑病的常染色体隐性遗传性脑动脉病的临床及基因诊断[J]. 中华神经科杂志, 2013, 46(4):217-219.
  HE Z Y. The clinical and genetic diagnosis of autosomal recessive inherited arteriopathy with subcortical infarcts and leukoencephalopathy should be given priority[J]. Chin J Neurol, 2013, 46(4):217-219.
[20] TRUEBESTEIN L, TENNSTAEDT A, M?NIG T, et al. Substrate-induced remodeling of the active site regulates human HTRA1 activity[J]. Nat Struct Mol Biol, 2011, 18(3):386-388.
[21] KONO Y, WAKABAYASHI T, KOBAYASHI M, et al. Characteristics of cerebral microbleeds in patients with Fabry disease[J]. J Stroke Cerebrovasc Dis, 2016, 25(6):1320-1325.
[22] LYNDON D, DAVAGNANAM I, WILSON D, et al. MRI-visible perivascular spaces as an imaging biomarker in Fabry disease[J]. J Neurol, 2021, 268(3):872-878.
[23] ZHANG C, LI Z, WANG Y, et al. Risk factors of cerebral microbleeds in strictly deep or lobar brain regions differed[J]. J Stroke Cerebrovasc Dis, 2015, 24(1):24-30.
[24] POELS M M, IKRAM M A, VAN DER LUGT A, et al. Incidence of cerebral microbleeds in the general population: the Rotterdam Scan Study[J]. Stroke, 2011, 42(3):656-661.
[25] 戴悦, 凤心雨, 戴昕妤, 等. 脑微出血及其分度的相关危险因素分析[J]. 国际神经病学神经外科学杂志, 2022, 49(1): 31-36.
  DAI Y, FENG X Y, DAI X Y, et al. Risk factors for cerebral microbleeds and its grading[J]. J Int Neurol Neurosurg, 2022, 49(1): 31-36.
[26] WU Y, CHEN T. An Up-to-Date Review on Cerebral Microbleeds[J]. J Stroke Cerebrovasc Dis, 2016, 25(6):1301-1306.
[27] 杨艳玲, 高世龙, 尤红, 等. 脑微出血相关危险因素回顾性研究[J]. 国际神经病学神经外科学杂志, 2018, 45(3):272-276.
  YANG Y L, GAO S L, YOU H, et al. A retrospective study of risk factors associated with cerebral microbleeds[J]. J Int Neurol Neurosurg, 2018, 45(3):272-276.
[28] WADI LC, GRIGORYAN M M, KIM R C, et al. Mechanisms of Cerebral Microbleeds[J]. J Neuropathol Exp Neurol, 2020, 42(2):1093-1099.
[29] QIU C, COTCH M F, SIGURDSSON S, et al. Retinal and cerebral microvascular signs and diabetes: the age, gene/environment susceptibility-Reykjavik study[J]. Diabetes, 2008, 57(6):1645-1650.
[30] MADONNA R, PIERAGOSTINO D, BALISTRERI CR, et al. Diabetic macroangiopathy: Pathogenetic insights and novel therapeutic approaches with focus on high glucose-mediated vascular damage[J]. Vascul Pharmacol, 2018, 6(17):S1537-1891.
[31] THORN L M, SHAMS S, GORDIN D, et al. Clinical and MRI features of cerebral small-vessel disease in type 1 diabetes[J]. Diabetes Care, 2019, 42(2):327-330.
[32] 田成林. 脑淀粉样血管病[J]. 中华神经科杂志, 2021, 54:(5):499-507.
  TIAN C L. Cerebral amyloid angiopathy[J]. Chin J Neurol, 2021, 54(5):499-507.
[33] DIERKSEN G A, SKEHAN M E, KHAN M A, et al. Spatial relation between microbleeds and amyloid deposits in amyloid angiopathy[J]. Ann Neurol, 2010, 68(4):545-548.
[34] ROMERO J R, PREIS S R, BEISER A, et al. Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study[J]. Stroke, 2014, 45(5):1492-1494.
[35] 乔亚男, 王磊, 邵文, 等. 脑微出血β淀粉样蛋白阳性患者载脂蛋白E基因型及认知特点[J]. 中华老年医学杂志, 2020, 39(5):489-492.
  QIAO Y N, WANG L, SHAO W, et al. Characteristics of apolipoprotein E genotype and cognitive impairment in patients with cerebral microbleeds and positive β amyloid[J]. Chin J Geriatr, 2020, 39(5):489-492.
[36] WANG B R, OU Z, JIANG T, et al. Independent correlation of serum homocysteine with cerebral microbleeds in patients with acute ischemic stroke due to large-artery atherosclerosis[J]. J Stroke Cerebrovasc Dis, 2016, 25(11):2746-2751.
[37] FENG C, BAI X, XU Y, et al. Hyperhomocysteinemia associates with small vessel disease more closely than large vessel disease[J]. Int J Med Sci, 2013, 10(4):408-412.
[38] RYU W S, KIM C K, KIM B J, et al. Serum uric acid leve-ls and cerebral microbleeds in patients with acute ische-mic stroke[J]. PLoS One, 2013, 8(1):e55210.
[39] SHIMA H, ISHIMURA E, NAGANUMA T, et al. Cerebral microbleeds in predialysis patients with chronic kidney disease[J]. Nephrol Dial Transplant, 2010, 25(5):1554-1559.
[40] QIAN Y, ZHENG K, WANG H, et al. Cerebral microbleeds and their influence on cognitive impairment in Dialysis patients[J]. Brain Imaging Behav, 2021, 15(1):85-95.
[41] NAGANUMA T, TAKEMOTO Y. Asymptomatic Cerebrovascular Disease in Dialysis Patients[J]. Contrib Nephrol, 2018, 196:22-26.
[42] HURNHER M M, BOBAN J, R?GGLA M, et al. Distinct pattern of microsusceptibility changes on brain magnetic resonance imaging (MRI) in critically ill patients on mechanical ventilation/oxygenation[J]. Neuroradiology, 2021, 63(10):1651-1658.
[43] HWANG J, CATUREGLI G, WHITE B, et al. Cerebral Microbleeds and Intracranial Hemorrhages in Adult Patients on Extracorporeal Membrane Oxygenation-Autopsy Study[J]. Crit Care Explor, 2021, 3(3):e0358.
[44] KIRSCHENBAUM D, IMBACH L L, RUSHING E J, et al. Intracerebral endotheliitis and microbleeds are neuropathological features of COVID-19[J]. Neuropathol Appl Neurobiol, 2021, 47(3):454-459.
[45] GARG R K, PALIWAL V K, MALHOTRA H S, et al. Neuroimaging Patterns in Patients with COVID-19-Associated Neurological Complications: A Review[J]. Neurol India, 2021, 69(2):260-271.
[46] NOORBAKHSH-SABET N, PULAKANTI VC, ZAND R. Uncommon causes of cerebral microbleeds[J]. J Stroke Cerebrovasc Dis, 2017, 26(10):2043-2049.
[47] KOO D L, KIM J Y, LIM J S, et al. Cerebral microbleeds on MRI in patients with obstructive sleep apnea[J]. J Clin Sleep Med, 2017, 13(1):65-72.
[48] 武秋娣, 晏晓慧, 吴旦, 等. 高血压合并脑微出血认知障碍特点及中医证型分析[J]. 中国临床研究, 2023, 36(3):334-338.
  WU Q D, YAN X H, WU D, et al. Characteristics of cognitive impairment and analysis of TCM syndrome differentiation in hypertensive patients with cerebral microbleed[J]. Chin J Clin Res, 2023, 36(3):334-338.
[49] WILSON D, AMBLER G, LEE K J, et al. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies[J]. Lancet Neurol, 2019, 18(7):653-665.
[50] AL-SHAHI SALMAN R, MINKS D P, MITRA D, et al. Effects of antiplatelet therapy on stroke risk by brain ima-ging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial[J]. Lancet Neurol, 2019, 18(7):643-652.
[51] SOO Y, ABRIGO J M, LEUNG K T, et al. Risk of intracerebral haemorrhage in Chinese patients with atrial fibrillation on warfarin with cerebral microbleeds: the IPAAC-Warfarin study[J]. J Neurol Neurosurg Psychiatry, 2019, 90(4):428-435.
[52] WILSON D, AMBLER G, SHAKESHAFT C, et al. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute is-chaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study[J]. Lancet Neurol, 2018, 17(6):539-547.
[53] CHENG Y, WANG Y, SONG Q, et al. Use of anticoagulant therapy and cerebral microbleeds: a systematic review and meta-analysis[J]. J Neurol, 2021, 268(5):1666-1679.
[54] STEFFEL J, COLLINS R, ANTZ M, et al. European Heart Rhythm Association Practical Guide on the use of non-Vitamin K antagonist oral anticoagulants in patients with atrial fibrillation[J]. Europace, 2021, 23(10):1612-1676.
[55] BRAEMSWIG T B, SCHLEMM L, THOMALLA G, et al. Author response: Cerebral microbleeds and treatment effect of intravenous thrombolysis in acute stroke: an analysis of the WAKE-UP randomized clinical trial[J]. Neurology, 2022, 98(19):817.
[56] DERRAZ I, CAGNAZZO F, GAILLARD N, et al. Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Endovascular Thrombectomy[J]. Neurology, 2021, 96(13):e1724-e1731.
[57] WU X, YAN J, YE H, et al. Pre-treatment cerebral microbleeds and intracranial hemorrhage in patients with ische-mic stroke receiving endovascular therapy: a systematic review and meta-analysis[J]. J Neurol, 2020, 267(5):1227-1232.
[58] XU T, WANG Y, YUAN J, et al. Small vessel disease burden and outcomes of mechanical thrombectomy in ischemic stroke: A systematic review and meta-analysis[J]. Front Neurol, 2021, 12:602037.
Outlines

/