Walls Of Cortical Vessels Research Articles

P.087 Successful response to rituximab in a patient with Aβ related angiitis

Background: Aβ-related angiitis (AβRA) is a rare presentation of cerebral amyloid angiopathy, where vasculitis results from an auto-immune reaction to amyloid deposits in leptomeningeal and cortical vessel walls. Anti-CD20 monoclonal antibodies, such as rituximab, have demonstrated efficacy in systemic small vessel vasculitides, particularly in refractory cases. The efficacy of rituximab in AβRA remains unknown. Methods: Patient chart, functional measures, and laboratory findings were reviewed from the time of patient admission until 12 months after discharge. Results: A 61-year-old man presented with headache and altered mental status. Brain MRI revealed multiple cortical infarcts, leptomeningeal enhancement, and cortical microbleeds, and brain biopsy ultimately confirmed the diagnosis of AβRA. The patient developed new ischemic lesions despite corticosteroid pulse, and intravenous cyclophosphamide was halted after four weeks due to iatrogenic acute hepatitis. Rituximab was initiated and led to sustained clinical improvement with no subsequent relapses. Maintenance therapy involved gradually tapered low-dose oral steroids and rituximab at 6- and 12-months post-induction. Conclusions: This report suggests that rituximab may be effective in inducing remission and preventing relapses in biopsy-proven case of AβRA. Controlled studies are needed to better assess the efficacy and tolerability of anti-CD20 antibodies in cerebral vasculitis.

Different microvascular alterations underlie microbleeds and microinfarcts.

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid β (Aβ) in the walls of cortical vessels and the accrual of microbleeds and microinfarcts over time. The relationship between CAA severity and microbleeds and microinfarcts as well as the sequence of events that lead to lesion formation remain poorly understood. We scanned intact formalin-fixed hemispheres of 12 CAA cases with magnetic resonance imaging (MRI), followed by histopathological examination in predefined areas and serial sectioning in targeted areas with multiple lesions. In total, 1,168 cortical microbleeds and 472 cortical microinfarcts were observed on ex vivo MRI. Increasing CAA severity at the whole-brain or regional level was not associated with the number of microbleeds or microinfarcts. However, locally, the density of Aβ-positive cortical vessels was lower surrounding a microbleed compared to a simulated control lesion, and higher surrounding microinfarcts. Serial sectioning revealed that for (n = 28) microbleeds, both Aβ (4%) and smooth muscle cells (4%) were almost never present in the vessel wall at the site of bleeding, but Aβ was frequently observed upstream or downstream (71%), as was extensive fibrin(ogen) buildup (87%). In contrast, for (n = 22) microinfarcts, vascular Aβ was almost always observed at the core of the lesion (91%, p < 0.001) as well as upstream or downstream (82%), but few vessels associated with microinfarcts had intact smooth muscle cells (9%). These observations provide a model for how a single neuropathologic process such as CAA may result in hemorrhagic or ischemic brain lesions potentially through 2 different mechanistic pathways. ANN NEUROL 2019;86:279-292.

Abstract 92: Detection of Radiologic and Laboratory Features of Cerebral Amyloid Angiopathy in Patients with Alzheimer’s Disease

Background: Patients with Cerebral Amyloid Angiopathy (CAA) have posterior vascular amyloid deposition and lower Amyloid Beta (Aβ) levels when compared to Alzheimer’s Disease (AD). We hypothesized that similar findings would be observed in AD patients with strictly lobar microbleeds (LMB) and/or cortical superficial siderosis (cSS) attributable to CAA [CAA-AD], when compared to AD with no hemorrhagic lesion [NH-AD]. Methods: We reviewed brain MRIs of patients with AD who had T2*-, FLAIR and 3D T1-weighted MRI as well as Florbetapir PET, CSF Aβ-42 and tau levels, and APOE status within the ADNI database. We compared the demographics, quantitative imaging and lab findings of CAA-AD to NH-AD. Results: The CAA-AD (n=51) and NH-AD (n=85) groups were balanced for age, gender and history of hypertension (all p&gt;0.2). The APOE4 was more frequently present in the CAA-AD group (78% vs 60%, p=0.038), no difference for APOE2 (p=0.41). Patients with CAA-AD had higher WMH volume (0.73 vs 0.49 % intracranial volume [ICV], p=0.035) and higher occipital-to-global Florbetapir ratio (0.98 vs 0.94, p=0.02) but similar mean cortical Florbetapir uptake (1.38 vs 1.36, p=0.57), cortical thickness (2.22 vs 2.20 mm, p=0.38), and hippocampal volume (0.37 vs 0.38 % of ICV, p=0.24) when compared to NH-AD. In a multivariable regression model that included all variables above, higher occipital-to-global Florbetapir ratio (p=0.009) and presence of APOE4 (p=0.002) were associated with CAA-AD, higher WMH (p=0.097) showed a trend. In 117 patients with CSF data, CAA-AD (n=46) had lower Aβ-42 (127 vs 140 pg/ml, p=0.038) but similar tau levels (131 vs 136 pg/ml, p=0.68) when compared to NH-AD. Lower Aβ-42 was associated with CAA-AD (p=0.024) in the relevant multivariate regression model. Conclusions: Over one-third of patients with AD displayed subtle hemorrhagic lesions in a CAA-pattern on MRI. When compared to NH-AD, they have higher occipital Florbetapir uptake suggesting vascular amyloid binding and lower CSF Aβ-42 levels that might be related to sequestering of amyloid in cortical vessel walls. These results support the possibility that advanced CAA commonly accompanies clinically diagnosed AD, contributing to dementia pathogenesis and potentially affecting clinical treatment decisions.

A case of cerebral amyloid angiopathy with reversible white matter lesions and multiple cerebral microbleeds

A 59-year-old woman presented with a 7-year history of headache. She showed no neurological abnormality. T(2) weighted magnetic resonance (MR) images showed a hyperintense signal in the white matter in the bilateral parieto-occipital lobe without abnormal enhancement. A small amount of prednisolone was administered for rheumatoid arthritis. After prednisolone was discontinued, the T(2) weighted images showed an expansion of the hyperintense signal lesions seen in the white matter, and T(2) weighted image showed multiple foci of petechial bleeding in the cortex and subcortex of the bilateral occipital lobe. A brain biopsy specimen from the right occipital lobe revealed deposition of amyloid in the subarachnoidal and cortical vessel walls and transmural infiltration of a few lymphocytes, eosinophils, and giant histiocytes. Subsequently the patient was diagnosed with central nervous system vasculitis associated with cerebral amyloid angiopathy (CAA). After 5 months, the T(2) weighted images showed a remarkable regression of the hyperintense signal lesions in the white matter of the bilateral parieto-occipital lobe without the administration of any maintenance immunosuppressive agents. However, T(2) weighted image showed an increase of multiple cortico-subcortical foci of petechial bleeding. Her headache did not improve during the illness. Thus, we should consider the diagnosis of CAA when patients present with reversible white matter lesions and multiple cerebral microbleeds simultaneously.