ARIA-E Severity Grading on MRI
ARIA-E severity is graded as mild, moderate, or severe based on standardized MRI scoring systems that assess the extent and distribution of parenchymal edema and sulcal effusions, with management decisions directly tied to these severity grades. 1
Severity Classification System
The most widely validated approach uses either a 3-point (SSAE-3) or 5-point (SSAE-5) severity scale based on the largest linear measurement of the lesion and its spatial dissemination 2:
Mild ARIA-E
- Limited parenchymal T2 FLAIR hyperintensity
- Minimal sulcal effusions
- No significant mass effect
- Typically asymptomatic 1
Moderate ARIA-E
- Intermediate extent of parenchymal edema
- Variable sulcal FLAIR hyperintensity
- May present with or without symptoms 1
- Requires close monitoring and possible treatment modification 1
Severe ARIA-E
- Extensive parenchymal involvement across multiple brain regions
- Significant mass effect on surrounding structures
- Typically symptomatic presentation (headache, confusion, visual disturbances) 1, 3
- Mandates treatment modification or discontinuation 1
Key Imaging Features to Assess
When grading ARIA-E severity, systematically evaluate 1:
- Anatomic location and distribution across the 6 brain regions bilaterally (frontal, parietal, temporal, occipital, basal ganglia/thalamus, cerebellum/brainstem) 4
- Extent of parenchymal T2 FLAIR hyperintensity - quantify the largest area of involvement 2
- Presence and extent of sulcal FLAIR hyperintensity (non-suppression of CSF signal) 1, 4
- Associated mass effect on surrounding structures 1
Validated Scoring Systems
SSAE-3 and SSAE-5 Scales
The 3-point and 5-point Severity Scales of ARIA-E have demonstrated excellent inter-reader reliability (Cohen's kappa 0.79 and 0.73 respectively) and are now used in most major Alzheimer's disease trials 2. These scales assign a 0-6 point score for each of 6 brain regions bilaterally, with total scores ranging 0-60 4.
The SSAE-3 is preferred for clinical practice as it provides adequate discrimination with simpler implementation compared to SSAE-5 2, 5.
Alternative: Barkhof Grand Total Scale (BGTS)
The BGTS correlates highly with SSAE scales, with high concordance when using SSAE-3 >1 corresponding to BGTS >3 (accuracy 0.85-0.93) 5. However, the SSAE scales are more practical for routine clinical use 2.
Technical MRI Requirements
Essential Sequences
All three sequences are mandatory for comprehensive ARIA assessment 1:
- T2 FLAIR - primary sequence for detecting ARIA-E 6, 1
- T2 GRE or SWI* - for concurrent ARIA-H detection 6, 1
- DWI - to exclude acute ischemia and assess for restricted diffusion 1, 3
Scanner Specifications
- Minimum field strength: 1.5T acceptable, though 3T provides greater sensitivity 6, 3
- Slice thickness: ≤5mm 6
- TE: ≥20ms for gradient echo sequences 6
Reading Standards and Pitfalls
Central Reading Preferred
Central reading by trained neuroradiologists with specific ARIA expertise is strongly preferred over local reads to ensure accuracy and inter-rater reliability 1. This is particularly important because:
- Subtle ARIA-E can be easily missed on routine reads 6
- Fulminant ARIA-E can be misidentified as subarachnoid hemorrhage or venous infarction 6
- Variable diagnostic certainty is inherent - allowance for "possible" vs "definite" readings should be made 6
Common Pitfalls to Avoid
- Do not exclude patients based on "possible" findings - only "definite" ARIA-E should trigger management changes 6
- Recognize that very subtle asymptomatic ARIA-E may not have clinical consequences if missed 6
- Serial MRI scans may be needed to change diagnostic confidence from "possible" to "definite" 6
Clinical Correlation
Management is determined by both MRI severity grade AND clinical symptoms, not MRI findings alone 1. Symptomatic moderate-to-severe ARIA-E may require corticosteroid treatment, while asymptomatic mild ARIA-E may only warrant closer monitoring 1, 3.