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Reduction of microbleeds by immunosuppression in a patient with Aβ-related vascular inflammation.

Traschütz A, Tzaridis T, Penner AH, Kuchelmeister K, Urbach H, Hattingen E, Heneka MT - Neurol Neuroimmunol Neuroinflamm (2015)

Bottom Line: Under long-term immunosuppressive treatment, a reduced number of cortical micobleeds was observed on repeat MRIs because of both the prevention of new microbleeds and the clearance of those existing at baseline.This study provides Class IV evidence.This is a single observational study without controls.

View Article: PubMed Central - PubMed

Affiliation: Departments of Neurology (A.T., T.T., M.T.H.), Neuroradiology (A.-H.P., E.H.), and Neuropathology (K.K.), University of Bonn, Germany; Department of Neuroradiology (H.U.), University of Freiburg, Germany; and German Center for Neurodegenerative Disease (M.T.H.), Bonn, Germany.

ABSTRACT

Objective: To investigate whether the occurrence or clearance of microhemorrhages in cerebral amyloid angiopathy (CAA)-related vascular inflammation can be modified by immunosuppressive treatment.

Methods: Clinical and radiologic follow-up for more than 5 years of a patient with histopathologically confirmed CAA-related vascular inflammation treated with a prolonged and tapered regimen of IV cyclophosphamide and oral steroids.

Results: Under long-term immunosuppressive treatment, a reduced number of cortical micobleeds was observed on repeat MRIs because of both the prevention of new microbleeds and the clearance of those existing at baseline.

Conclusions: Sustained immunosuppression should be considered and systematically investigated as a treatment option for cortical microbleeds in CAA and related inflammatory phenotypes.

Classification of evidence: This study provides Class IV evidence. This is a single observational study without controls.

No MeSH data available.


Related in: MedlinePlus

Pathologic diagnosis of CAA-related vascular inflammationHematoxylin & eosin staining (A) revealed focal intramural inflammation including lymphocytes, multinuclear giant cells, and surrounding reactive astrocytes. Vascular amyloid deposits in cortical and leptomeningeal vessels were seen on Congo red stain (B) and immunohistochemical stainings against β-amyloid (C). Staining against CD68 (D) highlights monocytic involvement. All images taken at 200×.
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Figure 2: Pathologic diagnosis of CAA-related vascular inflammationHematoxylin & eosin staining (A) revealed focal intramural inflammation including lymphocytes, multinuclear giant cells, and surrounding reactive astrocytes. Vascular amyloid deposits in cortical and leptomeningeal vessels were seen on Congo red stain (B) and immunohistochemical stainings against β-amyloid (C). Staining against CD68 (D) highlights monocytic involvement. All images taken at 200×.

Mentions: Upon progression of the fluid-attenuated inversion recovery (FLAIR) hyperintensities in a follow-up MRI 6 weeks later (figure 1), 2 brain biopsies were taken from the lesion in the right frontal lobe. Both specimens showed Congo red–positive thickening of cortical and leptomeningeal vessel walls accompanied by multiple acute microhemorrhages and focal hemosiderin deposits. Immunohistochemical stainings revealed multiple, mostly diffuse, Aβ deposits in the parenchyma but no evidence of tau pathology. The vessels with intramural Aβ deposits often showed perivascular or transmural inflammatory infiltrates, including CD3+, CD8+, and some CD20+ lymphocytes as well as CD68+ monocytes, multinucleated giant cells, and surrounding reactive astrocytes (figure 2). In some of these vessels, angiodestructive changes of their walls were seen. Based on these findings, a diagnosis of “cerebral Aβ angiitis” was made and immunosuppressive treatment was initiated with daily oral prednisone and pulses of IV cyclophosphamide (table).


Reduction of microbleeds by immunosuppression in a patient with Aβ-related vascular inflammation.

Traschütz A, Tzaridis T, Penner AH, Kuchelmeister K, Urbach H, Hattingen E, Heneka MT - Neurol Neuroimmunol Neuroinflamm (2015)

Pathologic diagnosis of CAA-related vascular inflammationHematoxylin & eosin staining (A) revealed focal intramural inflammation including lymphocytes, multinuclear giant cells, and surrounding reactive astrocytes. Vascular amyloid deposits in cortical and leptomeningeal vessels were seen on Congo red stain (B) and immunohistochemical stainings against β-amyloid (C). Staining against CD68 (D) highlights monocytic involvement. All images taken at 200×.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608757&req=5

Figure 2: Pathologic diagnosis of CAA-related vascular inflammationHematoxylin & eosin staining (A) revealed focal intramural inflammation including lymphocytes, multinuclear giant cells, and surrounding reactive astrocytes. Vascular amyloid deposits in cortical and leptomeningeal vessels were seen on Congo red stain (B) and immunohistochemical stainings against β-amyloid (C). Staining against CD68 (D) highlights monocytic involvement. All images taken at 200×.
Mentions: Upon progression of the fluid-attenuated inversion recovery (FLAIR) hyperintensities in a follow-up MRI 6 weeks later (figure 1), 2 brain biopsies were taken from the lesion in the right frontal lobe. Both specimens showed Congo red–positive thickening of cortical and leptomeningeal vessel walls accompanied by multiple acute microhemorrhages and focal hemosiderin deposits. Immunohistochemical stainings revealed multiple, mostly diffuse, Aβ deposits in the parenchyma but no evidence of tau pathology. The vessels with intramural Aβ deposits often showed perivascular or transmural inflammatory infiltrates, including CD3+, CD8+, and some CD20+ lymphocytes as well as CD68+ monocytes, multinucleated giant cells, and surrounding reactive astrocytes (figure 2). In some of these vessels, angiodestructive changes of their walls were seen. Based on these findings, a diagnosis of “cerebral Aβ angiitis” was made and immunosuppressive treatment was initiated with daily oral prednisone and pulses of IV cyclophosphamide (table).

Bottom Line: Under long-term immunosuppressive treatment, a reduced number of cortical micobleeds was observed on repeat MRIs because of both the prevention of new microbleeds and the clearance of those existing at baseline.This study provides Class IV evidence.This is a single observational study without controls.

View Article: PubMed Central - PubMed

Affiliation: Departments of Neurology (A.T., T.T., M.T.H.), Neuroradiology (A.-H.P., E.H.), and Neuropathology (K.K.), University of Bonn, Germany; Department of Neuroradiology (H.U.), University of Freiburg, Germany; and German Center for Neurodegenerative Disease (M.T.H.), Bonn, Germany.

ABSTRACT

Objective: To investigate whether the occurrence or clearance of microhemorrhages in cerebral amyloid angiopathy (CAA)-related vascular inflammation can be modified by immunosuppressive treatment.

Methods: Clinical and radiologic follow-up for more than 5 years of a patient with histopathologically confirmed CAA-related vascular inflammation treated with a prolonged and tapered regimen of IV cyclophosphamide and oral steroids.

Results: Under long-term immunosuppressive treatment, a reduced number of cortical micobleeds was observed on repeat MRIs because of both the prevention of new microbleeds and the clearance of those existing at baseline.

Conclusions: Sustained immunosuppression should be considered and systematically investigated as a treatment option for cortical microbleeds in CAA and related inflammatory phenotypes.

Classification of evidence: This study provides Class IV evidence. This is a single observational study without controls.

No MeSH data available.


Related in: MedlinePlus