Diagnosis Of Cerebral Amyloid Angiopathy-related Inflammation Research Articles

PS-R06-6: CEREBRAL AMYLOID ANGIOPATHY-RELATED INFLAMMATION PRESENTING WITH POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME

Background: Cerebral amyloid angiopathy related inflammation (CAAri) is a rare CAA variant, characterized by headaches, seizures, acute or subacute encephalopathy, or focal neurological deficits. Radiologically, CAAri presents with widespread white matter lesions on brain MRI in addition to the hemorrhagic imaging features of CAA. We report a patient with CAAri who showed posterior reversible encephalopathy syndrome. Case Report: A 77 year old man presented with generalized tonic clonic seizure that persisted for 30 minutes and decreased in consciousness level. He had past medical history of dementia, diabetes and hypertension. His initial blood pressure was 170/90 mmHg and pulse rates were 144/minute. On neurological examination, his consciousness level was stupor and there are no lateralizing signs. Cerebrospinal fluid analysis was unremarkable except elevated protein level of 75 mg/dL. Diffusion weighted images (DWI) and fluid attenuated inversion recovery (FLAIR) images showed diffuse hyperintensities involving the bilateral temporoparietooccipital lobes. Gradient echo images revealed multiple microbleeds in bilateral cortical and subcortical regions as can be seen in CAA. A diagnosis of CAAri was considered, and the patient was started on steroids and valproic acid with clinical improvement. Nine days after admission, follow up DWI and FLAIR images demonstrated improvement of previously shown lesions. Conclusions: Aside from the most common subacute presentations, CAAri can have a PRES like presentation. It is hypothesised that in this form, CAAri causes altered vascular autoregulation and impaired blood brain barrier integrity in the face of precipitating factors such as hypertension.

Cerebral Amyloid Angiopathy-Related Inflammation: Report of a Case with Very Difficult Therapeutic Management

Background. Cerebral amyloid angiopathy-related inflammation (CAA-ri) results from autoimmune response to beta-amyloid deposits in cerebral vessels. Its clinical course and complications have seldom been described in literature. Case Report. In a patient presenting with delirium and left hemiparesis the diagnosis of CAA-ri was supported by the finding of elevated anti-amyloid autoantibodies in the cerebrospinal fluid (CSF). Steroid therapy produced significant improvements in clinical and investigational assessments, but after two months, it caused Acute Respiratory Distress Syndrome. After steroid therapy discontinuation the patient presented a rapidly progressive dementia, Guillain-Barré syndrome, new cerebral ischemic lesions, and thrombosis of the right cephalic and subclavian veins that were treated with subcutaneous heparin. After a week the patient died because of brain hemorrhage. Conclusion. This case suggests caution in steroid therapy discontinuation and antithrombotic therapy administration in patients with CAA-ri. The CSF search of anti-amyloid autoantibodies could be helpful to support the diagnosis.

Abstract W MP89: Validation of Clinical-Radiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy-related Inflammation

Introduction: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a disease subtype characterized by rapidly progressive cognitive decline, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation. CAA-ri is an important diagnosis to reach in clinical practice, as many patients respond to immunosuppressive therapy. Definitive diagnosis of CAA-ri generally requires brain biopsy, however, highlighting the importance of developing noninvasive diagnostic criteria. Objectives: To test the sensitivity and specificity of modified criteria (Table 1) for possible and probable CAA-ri in groups of subjects with histologically proven CAA-ri and non-CAA-ri. Methods: After refining previously proposed clinical- radiological criteria we retrospectively analyzed clinical charts and MRI FLAIR and gradient-echo scans obtained from 17 subjects with pathologically confirmed CAA-ri and 37 control subjects with pathologic diagnosis of non-inflammatory CAA. The control group was further divided into those with past intracerebral hemorrhage (ICH) (n=21) and those with cerebral microbleeds (CMB) only and no history of ICH (n=16). Results: In the CAA-ri group 14/17 (82.4%) met criteria for both probable and possible CAA-ri. One (4.7%) of the subjects in the control CAA-ICH group (n=21) met the criteria for possible and none met criteria for probable CAA-ri. In the control CAA-no ICH group 1/16 (6.25%) and 11/16 (68.75%) met criteria for probable and possible CAA-ri respectively. This yields sensitivity and specificity of 82% and of 97.3% respectively for the probable criteria and sensitivity and specificity of 82% and 67.6% respectively for the possible criteria. Conclusions: Our data suggest that a reliable diagnosis of CAA-ri can be reached from basic clinical and radiographic information alone with good sensitivity and excellent specificity.

Corticosteroid therapy in a patient with cerebral amyloid angiopathy-related inflammation

We studied longitudinal changes of the levels of anti-amyloid β (anti-Aβ) antibody, amyloid β (Aβ) protein, and interleukin 8 (IL-8) in cerebrospinal fluid (CSF) of a patient with cerebral amyloid angiopathy-related inflammation (CAA-ri) in whom steroid treatment resulted in clinical improvement. The diagnosis of CAA-ri was established with brain biopsy. Levels of anti-Aβ 42 antibody, Aβ 40, Aβ 42 and IL-8 in CSF were measured in the CAA-ri patient at 23 time points in the 8-month clinical course. These CSF samples were divided into 2 groups: those obtained before (n = 12) and those after (n = 11) oral corticosteroid therapy was started. We compared these levels between CSF samples obtained before and after therapy. The mean levels of anti-Aβ 42 antibody and IL-8 were significantly higher in CSF samples of the CAA-ri patient before oral corticosteroid therapy than those after therapy. A positive correlation was noted between levels of anti-Aβ 42 antibodies and IL-8 in CSF of this patient. There were no significant differences of mean levels of Aβ 40 and Aβ 42 between CSF samples obtained before and after oral corticosteroid therapy. It was possible that the autoinflammatory process with anti-Aβ 42 antibodies and IL-8 may have been involved in the pathogenesis of CAA-ri, and that corticosteroid therapy directly affected levels of anti-Aβ 42 antibody and IL-8. In summary, CAA-ri encephalopathy is a relapsing or progressive disorder and may be treatable by adequate immunosuppressive therapy. The anti-Aβ 42 antibody in CSF is a useful biological marker for therapeutic monitoring of CAA-ri.