Amyloid beta related angiitis

Case Discussion

In the setting of cognitive impairment, the findings of convexal subarachnoid hemorrhage, cortical superficial siderosis, a profusion of strictly lobar microhemorrhages, and multispot white matter hyperintensities raised the possibility of cerebral amyloid angiopathy (probable CAA by Boston 2.0 criteria). The presence of numerous recent cortical-subcortical microinfarcts and parenchymal and leptomeningeal enhancement did not fit bland cerebral amyloid angiopathy, however, nor were they completely explained as sequelae of infarcts and subarachnoid hemorrhage. The absence of asymmetric white matter hyperintensity that extended to immediate subcortical white matter meant the case did not meet diagnostic criteria for cerebral amyloid angiopathy related inflammation. The differential included primary angiitis of the central nervous system, intravascular lymphoma, paraneoplastic vasculitis, infectious vasculitis and meningoencephalitis, cardioembolism, and thrombotic microangiopathy.

Additional workup was performed. Whole body FDG PET-CT, which did not reveal findings to suggest a systemic malignancy or systemic vasculitis. Digital subtraction angiography was performed, which did not reveal evidence of a vasculitis of the large and medium cerebral vessels.

Lumbar puncture laboratory analysis was negative for neoplastic cells by cytology and flow cytometry, various infectious agents (cryptococcus, West Nile virus, enterovirus, HHV-6, eastern equine virus, JC virus, varicella zoster virus, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, syphilis, tuberculosis), and various paraneoplastic and autoimmune encephalopathy autoantibodies (Mayo clinic panel). CSF chemistry showed elevated protein (207 mg/dL), normal glucose (63 mg/dL), and lymphocytic pleocytosis (12 cells/cu mm). The protein included elevated IgG CSF (24 mg/dL) and albumin (129 mg/dL). Additional studies were negative for prion disease (RT-QuIC, 14-3-3 protein, T-tau protein). CSF biomarkers for Alzheimer disease were indeterminate, showing reduced A-beta 42 to T-tau index (ATI) and normal levels of P-tau protein.

Biopsy was performed of right frontal cortex and superficial vessel and meninges.

Pathology:

• Amyloid-Beta Related Angiitis

• NOTE: Tissue sections show granulomatous inflammation surrounding hyalinized vessels involving brain parenchyma and leptomeninges. There is focal neuronal loss with vascular hyperplasia, gliosis, and macrophages, suggestive of prior ischemic changes. White matter shows axonal balloons. Immunostaining shows CD68-positive macrophages comprising the granulomatous inflammation around vessels and macrophages admixed in the brain parenchyma. Amyloid beta immunostaining and a Congo Red stain highlight amyloid deposition in the vessel walls. AFB and GMS stains are negative for mycobacterial and fungal organisms, respectively. Iba1 highlights microglial activation. CD20 shows rare small B cells in the inflammatory infiltrate, with more abundant non-CD20-positive, CD45-positive small lymphocytes. GFAP shows reactive gliosis and Olig2 does not highlight increased glial cellularity or significant nuclear atypia. A Ki67 proliferation index shows focal increases in brain parenchyma, which is in tissue associated with increased macrophage infiltration. P53 labels rare cells, predominantly in a vascular and perivascular distribution, but is not definitely labeling glial cells in the brain parenchyma.

Therefore, the final diagnosis was amyloid-beta related angiitis (ABRA), a form of inflammatory cerebral amyloid angiopathy. The patient was treated with cyclophosphamide and mental status returned to normal.