Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage

Sergi Martinez-Ramirez¹, Jose-Rafael Romero², Ashkan Shoamanesh³, Ann C McKee⁴, Ellis Van Etten⁵, Octavio Pontes-Neto⁵, Eric A Macklin⁶, Alison Ayres⁵, Eitan Auriel⁵, Jayandra J Himali⁷, Alexa S Beiser⁸, Charles DeCarli⁹, Thor D Stein¹⁰, Victor E Alvarez¹¹, Matthew P Frosch¹², Jonathan Rosand¹³, Steven M Greenberg⁵, M Edip Gurol⁵, Sudha Seshadri², Anand Viswanathan⁵

Affiliations

¹ Neurology Department, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, MA, USA; Escola de Postgrau, Autonomous University of Barcelona, Barcelona, Spain. Electronic address: srmartinez@mgh.harvard.edu.
² Department of Neurology, School of Medicine, Boston University, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA.
³ Neurology Department, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA.
⁴ Department of Neurology, School of Medicine, Boston University, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA; Department of Pathology, School of Medicine, Boston University, Boston, MA, USA; United States Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA, USA.
⁵ Neurology Department, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, MA, USA.
⁶ Department of Biostatistics, Massachusetts General Hospital, Boston, MA, USA.
⁷ NHLBI's Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
⁸ Department of Neurology, School of Medicine, Boston University, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
⁹ Department of Neurology, University of California-Davis, Sacramento, CA, USA.
¹⁰ Department of Pathology, School of Medicine, Boston University, Boston, MA, USA; United States Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA, USA.
¹¹ Department of Neurology, School of Medicine, Boston University, Boston, MA, USA; Center for the Study of Traumatic Encephalopathy, Boston University Alzheimer Disease Center, Boston, MA, USA.
¹² Neuropathology Service, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charlestown, MA, USA.
¹³ Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.

PMID: 26079413
PMCID: PMC4677060
DOI: 10.1016/j.jalz.2015.04.009

Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage

Sergi Martinez-Ramirez et al. Alzheimers Dement. 2015 Dec.

. 2015 Dec;11(12):1480-1488.

doi: 10.1016/j.jalz.2015.04.009. Epub 2015 Jun 13.

Authors

Affiliations

¹ Neurology Department, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, MA, USA; Escola de Postgrau, Autonomous University of Barcelona, Barcelona, Spain. Electronic address: srmartinez@mgh.harvard.edu.
² Department of Neurology, School of Medicine, Boston University, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA.
³ Neurology Department, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA.
⁴ Department of Neurology, School of Medicine, Boston University, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA; Department of Pathology, School of Medicine, Boston University, Boston, MA, USA; United States Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA, USA.
⁵ Neurology Department, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, MA, USA.
⁶ Department of Biostatistics, Massachusetts General Hospital, Boston, MA, USA.
⁷ NHLBI's Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
⁸ Department of Neurology, School of Medicine, Boston University, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
⁹ Department of Neurology, University of California-Davis, Sacramento, CA, USA.
¹⁰ Department of Pathology, School of Medicine, Boston University, Boston, MA, USA; United States Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA, USA.
¹¹ Department of Neurology, School of Medicine, Boston University, Boston, MA, USA; Center for the Study of Traumatic Encephalopathy, Boston University Alzheimer Disease Center, Boston, MA, USA.
¹² Neuropathology Service, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charlestown, MA, USA.
¹³ Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.

PMID: 26079413
PMCID: PMC4677060
DOI: 10.1016/j.jalz.2015.04.009

Abstract

Introduction: The Boston criteria are the basis for a noninvasive diagnosis of cerebral amyloid angiopathy (CAA) in the setting of lobar intracerebral hemorrhage (ICH). We assessed the accuracy of these criteria in individuals with lobar microbleeds (MBs) without ICH.

Methods: We identified individuals aged >55 years having brain magnetic resonance imaging (MRI) and pathological assessment of CAA in a single academic hospital and a community-based population (Framingham Heart Study [FHS]). We determined the positive predictive value (PPV) of the Boston criteria for CAA in both cohorts, using lobar MBs as the only hemorrhagic lesion to fulfill the criteria.

Results: We included 102 individuals: 55 from the hospital-based cohort and 47 from FHS (mean age at MRI 74.7 ± 8.5 and 83.4 ± 10.9 years; CAA prevalence 60% and 46.8%; cases with any lobar MB 49% and 21.3%; and cases with ≥2 strictly lobar MBs 29.1% and 8.5%, respectively). PPV of "probable CAA" (≥2 strictly lobar MBs) was 87.5% (95% confidence interval [CI], 60.4-97.8) and 25% (95% CI, 13.2-78) in hospital and general populations, respectively.

Discussion: Strictly lobar MBs strongly predict CAA in non-ICH individuals when found in a hospital context. However, their diagnostic accuracy in the general population appears limited.

Keywords: Boston criteria; Cerebral amyloid angiopathy; Intracerebral hemorrhage; Likelihood ratio; Microbleed; Predictive value; Sensitivity; Specificity.

PubMed Disclaimer

Figures

**Figure 1**
Inclusion/exclusion workflow for hospital-based cases

See this image and copyright information in PMC

Comment in

Establishing the "meaning" of microbleeds: Clinical context or lobar microbleed burden?
Wilson D, Werring DJ. Wilson D, et al. Alzheimers Dement. 2016 Jan;12(1):85-6. doi: 10.1016/j.jalz.2015.09.004. Epub 2015 Oct 26. Alzheimers Dement. 2016. PMID: 26515762 No abstract available.

References

1. Pantelakis S. [A particular type of senile angiopathy of the central nervous system: congophilic angiopathy, topography and frequency] Monatsschr Psychiatr Neurol. 1954;128:219–256. - PubMed
1. Okazaki H, Reagan TJ, Campbell RJ. Clinicopathologic studies of primary cerebral amyloid angiopathy. Mayo Clin Proc. 1979;54:22–31. - PubMed
1. Vinters HV. Cerebral amyloid angiopathy. A critical review. Stroke; a journal of cerebral circulation. 1987;18:311–324. - PubMed
1. Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology. 2001;56:537–539. - PubMed
1. Ishihara T, Takahashi M, Yokota T, et al. The significance of cerebrovascular amyloid in the aetiology of superficial (lobar) cerebral haemorrhage and its incidence in the elderly population. J Pathol. 1991;165:229–234. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage

Affiliations

Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage

Authors

Affiliations

Abstract

Figures

Comment in

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Miscellaneous