Clinical and Paraclinical Measures Associated with Outcome in Cerebral Amyloid Angiopathy with Related Inflammation

Abstract

Background: Cerebral amyloid angiopathy with related inflammation (CAA-ri) is a rare age-associated disorder characterized by an inflammatory response to amyloid in cerebral blood vessels. CAA-ri is often treated with corticosteroids, but response to treatment is variable. Objective: To assess the relationship between clinical and paraclinical measures and outcomes in patients with CAA-ri treated with high doses of methylprednisolone. Methods: Longitudinal clinical course, and results from serum and cerebrospinal fluid (CSF) testing, electroencephalography, and neuroimaging were reviewed from 11 prospectively-accrued CAA-ri patients diagnosed, treated, and followed at Barnes Jewish Hospital (St. Louis, MO, USA). Magnetic resonance imaging (MRI) changes were quantified using a scoring system validated in cases of amyloid related imaging abnormality (ARIA-E). Clinical outcomes were assessed as change in modified Rankin Scale (ΔmRS) from baseline to final assessment (median 175 days from treatment with high doses of methylprednisolone; range, 31–513). Results: Worse outcomes following methylprednisolone treatment were associated with requirement for intensive care unit admission (median ΔmRS, 5 versus 1.5; p = 0.048), CSF pleocytosis (median ΔmRS 4.5 versus 1; p = 0.04), or lower CSF Aβ 40 at presentation (rho = –0.83; p = 0.02), and diffusion restriction (median ΔmRS 4 versus 1.5; p = 0.03) or higher late ARIA-E scores (rho = 0.70; p = 0.02) on MRI, but not preexisting cognitive decline (median ΔmRS 2 versus 2; p = 0.66). Conclusion: Clinical and paraclinical measures associated with outcomes may inform clinical counseling and treatment decisions in patients with CAA-ri. Baseline cognitive status was not associated with treatment responsiveness.

Amyloid‐Related Imaging Abnormalities in the DIAN‐TU‐001 Trial of Gantenerumab and Solanezumab: Lessons from a Trial in Dominantly Inherited Alzheimer Disease

“…During clinical trials, individuals who develop ARIA‐E while receiving a placebo may in fact be experiencing disease‐related spontaneous events such as cerebral amyloid angiopathy‐related inflammation (CAA‐ri). These findings, radiographically identical to drug‐related ARIA‐E, can be observed without treatment in DIAD and sporadic AD populations although they are relatively rare 32, 33 …”

“…These findings, radiographically identical to drug-related ARIA-E, can be observed without treatment in DIAD and sporadic AD populations although they are relatively rare. 32,33 We observed that most of the first incident ARIA-E occurred at gantenerumab doses higher than 675 mg. This is consistent with dose-dependency observed in previous clinical trials of gantenerumab and several other anti-amyloid monoclonal antibody drugs.…”

Rapidly Progressive Dementia

“…Patients with cerebral amyloid angiopathy with related inflammation typically present with RPD, with symptoms arising over weeks to months and focal signs localizing to affected brain regions. Advances in neuroimaging allow the diagnosis to be made with a high degree of certainty in most patients (revealing asymmetric white matter lesions associated with microscopic or macroscopic hemorrhages), 97 with further support from CSF biomarkers confirming low Aβ40 and Aβ42 and elevations in phosphorylated tau 98 . Biopsy may still be required to establish the diagnosis in patients with inconsistent or atypical imaging findings 99 .…”

“…Biopsy may still be required to establish the diagnosis in patients with inconsistent or atypical imaging findings 99 . Clinical and biomarker features associated with favorable responses to treatment and long-term prognoses continue to be recognized 98,100 …”

“…Advances in neuroimaging allow the diagnosis to be made with a high degree of certainty in most patients (revealing asymmetric white matter lesions associated with microscopic or macroscopic hemorrhages), 97 with further support from CSF biomarkers confirming low Aβ40 and Aβ42 and elevations in phosphorylated tau. 98 Biopsy may still be required to establish the diagnosis in patients with inconsistent or atypical imaging findings. 99 Clinical and biomarker features associated with favorable responses to treatment and long-term prognoses continue to be recognized.…”