2026 American Academy of Neurology Abstract Website

Objective:

This study aimed to characterize cerebral microangiopathy patterns and establish diagnostic imaging biomarkers for DADA2.

Background:

Neuroimaging phenotypes remain poorly characterized in patients with deficiency of adenosine deaminase 2 (DADA2).

Design/Methods:

We retrospectively analyzed consecutively enrolled DADA2 patients with neurological involvement from two ongoing prospective cohorts. The demographic, clinical, and neuroimaging data were evaluated, focusing on neuroimaging lesion patterns and cerebral small vessel disease (CSVD) imaging markers.

Results:

Thirteen patients were included, with 69.2% males. The median age at neurological onset was 17 (7-26) years. A striking disparity emerged between acute ischemic burden and chronic small vessel injury markers. During a follow-up of 51 (0.5-193) months, a total of 138 ischemic lesions were observed in all patients, primarily involving the pons (38 lesions), thalamus (21 lesions), internal capsule (20 lesions), and basal ganglia (18 lesions). Conversely, only one cerebral microbleed (CMB) was detected in all patients. Mild white matter hyperintensities (WMH) were observed in 9 patients. Infratentorial atrophy was prevailing and present in 69.2% (n=9) patients. Additionally, hemorrhagic stroke was less frequent (n=6, 46.2%) than infarction.

Conclusions:

DADA2 exhibited a high risk of stroke recurrence, with substantial asymptomatic lesions, suggesting the importance of routine neuroimaging evaluation for DADA2 patients. DADA2 presents a unique CSVD phenotype characterized by brainstem-deep gray nucleus ischemic predominance and infratentorial atrophy yet demonstrates paradoxically low burdens of CMBs and WMH compared to other CSVD. This distinctive imaging triad not only facilitates early recognition and timely intervention, but also suggests a pathophysiological divergence from other CSVD.