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Cortical microinfarcts in patients with multiple lobar microbleeds on 3 T MRI

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Abstract

The pathogenesis of cortical microinfarcts (CMIs) is considered to be heterogeneous including cerebral small vessel disease (SVD) such as hypertensive vasculopathy (HV) and cerebral amyloid angiopathy (CAA). Recent advances in MRI have enabled the detection of CMIs in vivo. To investigate the characteristics of CMIs in advanced cerebral SVD, we performed a retrospective analysis of 85 patients with cognitive impairment who had multiple lobar cerebral microbleeds (CMBs) on 3 T MRI. Among them, 41 (48.2%) patients were classified into the strictly lobar CMB group (i.e. probable-CAA group), and 44 (51.8%) patients were classified into the non-lobar with lobar CMBs group (i.e. mix-CMBs group). The relationship between CMIs and CMBs, cortical superficial siderosis (cSS) and white matter hyperintensity was evaluated. Nine of the 41 (22.0%) patients with probable-CAA had a total of 19 CMIs, while 12 of the 44 (27.3%) patients with mix-CMBs had a total of 38 CMIs. In the probable-CAA group, the presence of CMIs was significantly associated with the presence of cSS (p < 0.001). In addition, a close spatial association between CMIs and cSS was observed. On the contrary, in the mix-CMB group, the presence of CMIs was significantly associated with the number of lobar CMBs in the frontal lobe (p = 0.034). Our results suggest that CMIs in the probable-CAA may be attributable to more severe CAA, while CMIs in the mix-CMBs indicate an advanced HV, especially when observed with more numerous lobar CMBs.

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References

  1. Brundel M, de Bresser J, van Dillen JJ, Kappelle LJ, Biessels GJ (2012) Cerebral microinfarcts: a systematic review of neuropathological studies. J Cereb Blood Flow Metab 32:425–436

    Article  PubMed  PubMed Central  Google Scholar 

  2. van Veluw SJ, Shih AY, Smith EE, Chen C, Schneider JA, Wardlaw JM, Greenberg SM, Biessels GJ (2017) Detection, risk factors, and functional consequences of cerebral microinfarcts. Lancet Neurol 16:730–740

    Article  PubMed  PubMed Central  Google Scholar 

  3. Deramecourt V, Slade JY, Oakley AE, Perry RH, Ince PG, Maurage CA, Kalaria RN (2012) Staging and natural history of cerebrovascular pathology in dementia. Neurology 78:1043–1050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Charidimou A, Boulouis G, Gurol ME, Ayata C, Bacskai BJ, Frosch MP, Viswanathan A, Greenberg SM (2017) Emerging concepts in sporadic cerebral amyloid angiopathy. Brain 140:1829–1850

    Article  PubMed  PubMed Central  Google Scholar 

  5. Linn J, Halpin A, Demaerel P, Ruhland J, Giese AD, Dichgans M, van Buchem MA, Bruckmann H, Greenberg SM (2010) Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 74:1346–1350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Martinez-Ramirez S, Romero JR, Shoamanesh A, McKee AC, Van Etten E, Pontes-Neto O, Macklin EA, Ayres A, Auriel E, Himalli JJ et al (2015) Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage. Alzheimers Dement 11:1480–1488

    Article  PubMed  PubMed Central  Google Scholar 

  7. Greenberg SM, Charidimou A (2018) Diagnosis of cerebral amyloid angiopathy: evolution of the Boston criteria. Stroke 49:491–497

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gouw AA, Seewann A, van der Flier WM, Barkhof F, Rosemller AM, Scheltens P, Geurts JJ (2011) Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry 82:126–135

    Article  PubMed  Google Scholar 

  9. Park JH, Seo SW, Kim C, Kim GH, Noh HJ, Kim ST, Kwak KC, Yoon U et al (2013) Pathogenesis of cerebral microbleeds: in vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment. Ann Neurol 73:584–593

    Article  CAS  PubMed  Google Scholar 

  10. Kim YJ, Kim HJ, Park JH, Kim S, Woo SY, Kwak KC, Lee JM, Jung NY et al (2016) Synergistic effects of longitudinal amyloid and vascular changes on lobar microbleeds. Neurology 87:1575–1582

    Article  CAS  PubMed  Google Scholar 

  11. Ii Y, Maeda M, Kida H, Matsuo K, Shindo A, Taniguchi A, Tomimoto H (2013) In vivo detection of cortical microinfarcts on ultrahigh-field MRI. J Neuroimaging 23:28–32

    Article  PubMed  Google Scholar 

  12. Niwa A, Ii Y, Shindo A, Matsuo K, Ishikawa H, Taniguchi A, Takase S, Maeda M, Sakuma H, Akatsu H, Hashizume Y, Tomimoto H (2017) Comparative analysis of cortical microinfarcts and microbleeds using 3.0-Tesla postmortem magnetic resonance images and histopathology. J Alzheimers Dis 59:951–959

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ishikawa H, Ii Y, Niwa A, Shindo A, Ito A, Matsuura K, Sasaki R, Uno K, Maeda M, Tomimoto H (2018) Comparison of premortem magnetic resonance imaging and postmortem autopsy findings of a cortical microinfarct. J Stroke Cerebrovasc Dis 27:2623–2626

    Article  PubMed  Google Scholar 

  14. van Dalen JW, Scuric EE, van Veluw SJ, Caan MW, Nederveen AJ, Biessels GJ, van Gool WA, Richard E (2015) Cortical microinfarcts detected in vivo on 3 Tesla MRI: clinical and radiological correlates. Stroke 46:255–257

    Article  PubMed  Google Scholar 

  15. van Veluw SJ, Hilal S, Kuijf HJ, Ikram MK, Xin X, Yeow TB, Venketasubramanian N, Biessels GJ, Chen C (2015) Cortical microinfarcts on 3 T MRI: clinical correlates in memory-clinic patients. Alzheimers Dement 11:1500–1509

    Article  PubMed  Google Scholar 

  16. Ueda Y, Satoh M, Tabei K, Kida H, Ii Y, Asahi M, Maeda M, Sakuma H, Tomimoto H (2016) Neuropsychological features of microbleeds and cortical microinfarct detected by high resolution magnetic resonance imaging. J Alzheimers Dis 53:315–325

    Article  PubMed  Google Scholar 

  17. Hilal S, Sikking E, Shaik MA, Chan QL, van Veluw SJ, Vrooman H, Cheng CY, Sabanayagam C et al (2016) Cortical cerebral microinfarcts on 3 T MRI: a novel marker of cerebrovascular disease. Neurology 87:1583–1590

    Article  PubMed  Google Scholar 

  18. van den Brink H, Zwiers A, Switzer AR, Charlton A, MaCreary CR, Goodyear BG, Frayne R, Biessels GJ, Smith EE (2018) Cortical microinfarcts on 3 T magnetic resonance imaging in cerebral amyloid angiopathy. Stroke 49:1899–1905

    Article  PubMed  Google Scholar 

  19. Xiong L, van Veluw SJ, Bounemia N, Charidimou A, Pasi M, Boulouis G, Reijmer YD, Giese AK et al (2018) Cerebral cortical microinfarcts on magnetic resonance imaging and their association with cognition in cerebral amyloid angiopathy. Stroke 49:2330–2336

    Article  PubMed  PubMed Central  Google Scholar 

  20. van Rooden S, Goos JD, van Opstal AM, Versluis MJ, Webb AG, Blauw GJ, van der Flier WM, Scheltens P et al (2014) Increased number of microinfarcts in Alzheimer disease at 7-T MR imaging. Radiology 270:205–211

    Article  PubMed  Google Scholar 

  21. van Veluw SJ, Heringa SM, Kuijf HJ, Koek HL, Luijten PR, Biessels GJ (2014) Cerebral cortical microinfarcts at 7 Tesla MRI in patients with early Alzheimer's disease. J Alzheimers Dis 39:163–167

    Article  PubMed  Google Scholar 

  22. Fazekas F, Kleinert R, Roob G, Kleinert G, Kapeller P, Schmidt R, Hartung HP (1999) Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. AJNR Am J Neuroradiol 20:637–642

    CAS  PubMed  PubMed Central  Google Scholar 

  23. MaKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force of Alzheimer’s disease. Neurology 34:939–944

    Article  Google Scholar 

  24. Bruandet A, Richard F, Bombois S, Mauraqe CA, Deramecourt V, Lebett F, Amouyel P, Pasqueir F (2009) Alzheimer’s disease with cerebrovascular disease and vascular dementia: clinical features and course compared with Alzheimer’s diease. J Neurol Neurosurg Psychiatry 80:133–139

    Article  CAS  PubMed  Google Scholar 

  25. Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Bäckman L, Albert M, Almkvist O et al (2004) Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256:240–246

    Article  CAS  PubMed  Google Scholar 

  26. Román GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A et al (1993) Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43:250–260

    Article  PubMed  Google Scholar 

  27. Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindlei RI, O’Brien JT, Barkhof F, Benavente OR et al (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 12:822–838

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gregoire SM, Chaudhary UJ, Brown MM, Yousry TA, Kallis C, Jäger HR, Werring DJ (2009) The microbleed anatomical rating scale (MARS): reliability of a tool to map brain microbleeds. Neurology 73:1759–1766

    Article  CAS  PubMed  Google Scholar 

  29. Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjögren M, Wallin A, Ader H, Leys D, Pantoni L et al (2001) A new rating scale for aging-related white matter changes applicable to MRI and CT. Stroke 32:1318–1322

    Article  CAS  PubMed  Google Scholar 

  30. Charidimou A, Linn J, Vernooij MW, Opherkr HR, Akoudad S, Baron JC, Greenberg SM, Jäger HR, Werring DJ (2015) Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions. Brain 138:2126–2139

    Article  PubMed  Google Scholar 

  31. Okamoto Y, Yamamoto T, Kalaria RN, Senzaki H, Maki T, Hase Y, Kitamura A, Washida K, Yamada M, Ito H, Tomimoto H, Takahashi R, Ihara M (2012) Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts. Acta Neuropathol 123:381–394

    Article  CAS  PubMed  Google Scholar 

  32. Olichney JM, Ellis RJ, Katzman R, Sabbagh MN, Hansen L (1997) Types of cerebrovascular lesions associated with severe cerebral amyloid angiopathy in Alzheimer’s disease. Ann N Y Acad Sci 826:493–497

    Article  CAS  PubMed  Google Scholar 

  33. Soontornniyomkij V, Lynch MD, Mermash S, Pomakian J, Badkoobehi H, Clare R, Vinters HV (2010) Cerebral microinfarcts associated with severe cerebral beta-amyloid angiopathy. Brain Pathol 20:459–467

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  35. Lauer A, van Veluw SJ, William CM, Charidimou A, Roongpiboonsopit D, Vashkevich A, Ayres A, Martinez-Ramirez S, Gurol EM, Biessels GJ et al (2016) Microbleeds on MRI are associated with microinfarcts on autopsy in cerebral amyloid angiopathy. Neurology 87:1488–1492

    Article  PubMed  PubMed Central  Google Scholar 

  36. van Veluw SJ, Biessels GJ, Klijn CJ, Rozemuller AJ (2016) Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy. Neurology 86:867–871

    Article  CAS  PubMed  Google Scholar 

  37. De Reuck J, Deramecourt V, Cordonnier C, Auger F, Durieux N, Pasquier F, Bordet R, Defebvre L, Caparros-Lefebvre D, Maurage CA, Leys D (2013) Superficial siderosis of the central nervous system: a post-mortem 7.0-Tesla magnetic resonance imaging study with neuropathological correlates. Cerebrovasc Dis 36:412–417

    Article  PubMed  Google Scholar 

  38. De Reuck J, Deramecourt V, Auger F, Durieux N, Cordonnier C, Devos D, Defebvre L, Moreau C, Caparros-Lefebvre D, Bordet R, Maurage CA, Pasquier F, Leys D (2014) Post-mortem 7.0-tesla magnetic resonance study of cortical microinfarcts in neurodegenerative disease and vascular dementia with neuropathological correlates. J Neurol Sci 346:85–89

    Article  PubMed  Google Scholar 

  39. Pasi M, Charidimou A, Boulouis G, Auriel E, Ayres A, Schwab KM, Goldstein JN, Rosand J, Viswanasan A, Pantoni L, Greenberg SM, Gurol ME (2018) Mixed-location cerebral hemorrhage/microbleeds: underlying microangiopathy and recurrence risk. Neurology 90:e119–e126

    Article  PubMed  PubMed Central  Google Scholar 

  40. Thal DR, Ghebremedhin E, Orantes M, Wiestler OD (2003) Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline. J Neuropathol Exp Neurol 62:1287–1301

    Article  PubMed  Google Scholar 

  41. Kövari E, Herrmann FR, Gold G, Hof PR, Charidimou A (2017) Association of cortical microinfarcts and cerebral small vessel pathology in the ageing brain. Neuropathol Appl Neurobiol 43:505–513

    Article  CAS  PubMed  Google Scholar 

  42. Thomas T, Miners S, Love S (2015) Post-mortem assessment of hypoperfusion of cerebral cortex in Alzheimer’s disease and vascular dementia. Brain 138:1059–1069

    Article  PubMed  Google Scholar 

  43. Westover MB, Bianchi MT, Yang C, Schneider JA, Greenberg SM (2013) Estimating cerebral microinfarct burden from autopsy samples. Neurology 80:1365–1369

    Article  PubMed  PubMed Central  Google Scholar 

  44. Charidimou A, Farid K, Baron JC (2017) Amyloid-PET in sporadic amyloid angiopathy: a diagnostic accuracy meta-analysis. Neurology 89:1490–1498

    Article  PubMed  Google Scholar 

  45. Renard D, Castelnovo G, Wacongne A, Le Floch A, Thouvenot E, Mas J, Gabelle A, Labauge P, Lehmann S (2012) Interest of CSF biomarker analysis in possible cerebral amyloid angiopathy cases defined by the modified Boston criteria. J Neurol 259:2429–2433

    Article  CAS  PubMed  Google Scholar 

  46. Landi D, Maggio P, Lupoi P, Palazzo P, Altamura C, Falato E, Altavilla R, Vollaro S, Coniglio AD, Tibuzzi F et al (2015) Cortical ischemic lesion burden measured by DIR is related to carotid artery disease severity. Cerebrovasc Dis 39:23–30

    Article  PubMed  Google Scholar 

  47. Takasugi J, Miwa K, Watanabe Y, Okazaki S, Todo K, Sasaki T, Sakaguchi M, Mochizuki H (2019) Cortical cerebral microinfarcts on 3 T magnetic resonance imaging in patients with carotid artery stenosis. Stroke 50:639–644

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Yuichiro Ii, Hidehiro Ishikawa, Ai Ito, Ko Matsuo, Akihiro Shindo, Atsushi Niwa, Akira Taniguchi & Hidekazu Tomimoto

  2. Department of Advanced Diagnostic Imaging, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    Masayuki Maeda

  3. Department of Radiology, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    Maki Umino

  4. Department of Dementia Prevention and Therapeutics, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    Hirotaka Kida & Masayuki Satoh

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  1. Yuichiro Ii
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Correspondence to Yuichiro Ii.

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This study was approved by the ethical review board of Mie University Hospital and the requirement for written informed consent was waived because of the retrospective study design. This study was conducted in accordance with the ethical standards established in the 1964 Declaration of Helsinki and its subsequent amendments.

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Ii, Y., Maeda, M., Ishikawa, H. et al. Cortical microinfarcts in patients with multiple lobar microbleeds on 3 T MRI. J Neurol 266, 1887–1896 (2019). https://doi.org/10.1007/s00415-019-09350-9

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  • DOI: https://doi.org/10.1007/s00415-019-09350-9

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