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Advanced Neurology Insights on ARIA

targeting monoclonal antibodies probably strengthens cognitive decline, clinicians should immediately conduct
the neuroinflammatory response and leads to vascular a clinical evaluation and obtain further brain MRI scans
damage, thus mimicking the manifestations of CAA-ri. if necessary . Notably, it is recommended that the same
[24]
MRI equipment be used for evaluation throughout the
5. Administration of ARIA process and that radiologists receive ARIA-related training.

5.1. Severity classification For patients with radiographic findings of ARIA,
enhanced clinical vigilance is recommended. Additional
According to the prescribing information of aducanumab , MRI scans may be considered if clinically indicated. If
[49]
the severity of ARIA-E or ARIA-H can be classified into
three categories on MRI: mild, moderate, and severe. Mild radiographically severe ARIA-H is observed, treatment
ARIA-E shows FLAIR hyperintensity confined to the sulcus may be continued with caution only after a clinical
and/or cortex/subcortical white matter in one location, with evaluation is completed and a follow-up MRI demonstrates
radiographic stabilization (i.e., no increase in size or
a diameter <5 cm. Moderate ARIA-E requires a diameter of
FLAIR hyperintensity of 5–10 cm or more than one site of number of ARIA-H). For ARIA-E or mild/moderate
involvement, with each measuring <10 cm. Severe ARIA-E ARIA-H, treatment may continue with caution. If dosing
requires FLAIR hyperintensity that measures >10 cm is temporarily suspended, dosing may then resume at the
same dose and titration schedule. There are no systematic
and often requires substantial subcortical white matter data on continued dosing with aducanumab following the
and/or sulcal involvement; moreover, the lesions are likely
to involve one or more separate sites. The classification of detection of radiographically moderate or severe ARIA.
ARIA-H is based on the number of lesions. Specifically, Notably, the clinical severity and subjective feelings of
mild ARIA-H (microhemorrhage) is defined by ≤4 newly patients also need to be taken into account in the decision-
making process. In addition, more evidence is needed to
discovered microhemorrhages, the moderate type requires
5–9 newly discovered microhemorrhages, and the severe be able to assess the correlations between imaging findings
type is defined by ≥10 new microhemorrhages. Moreover, and clinical symptoms.
the number of local areas of superficial siderosis required 6. Conclusion
to define the three types of ARIA-H (superficial siderosis)
is 1, 2, and >2, respectively. Notably, the aforementioned Although controversy exists regarding the effectiveness of
standards are based on foreign recommendations, and aducanumab [50-52] , we believe that aducanumab represents
Chinese experts may need to modify the standards by a good start for future disease-modifying therapies. For
adapting them to the actual situation after accumulating example, the approval of tacrine paved the way for the
some experience. subsequent approval of other cholinesterase inhibitors,
although the use of tacrine has now been abandoned.
5.2. ARIA monitoring Thus, in the near future, an increasing number of specific
At present, there are no clinical practice guidelines for the anti-Aβ immunotherapies are likely to be approved [17,20] . At
management of ARIA. Aducanumab is the only amyloid- present, the application of amyloid-targeting monoclonal
targeting monoclonal antibody approved by the FDA; antibodies should be carried out in a tertiary medical
thus, the present consensus also refers to the prescribing center with a lot of clinical experience with AD because
information of aducanumab . Before starting treatment, ARIA is an unavoidable adverse event. Clinicians and
[49]
clinicians should obtain the latest baseline brain MRI radiologists should be familiar with ARIA, and it is very
scans of each patient so that clinical evaluations and important that different departments jointly diagnose and
comparisons can be made with the follow-up images after manage diseases. Most of the current data about ARIA
the medication has been taken. After treatment initiation, come from Western countries, and whether these data
the clinician should obtain brain MRIs before the seventh can be directly translated to the Chinese context warrants
(first dose of 10 mg/kg) and twelfth (sixth dose of 10 mg/ further research. Although the present consensus fills the
kg) infusion of aducanumab to look for the presence of knowledge gap of ARIA in China, it will need updating at
asymptomatic ARIA. It is suggested that clinicians should some point in the future, once a modified research data or
be extra vigilant for ARIA during the first eight infusions of management protocol has been proposed.
aducanumab, and especially during the titration period. If Acknowledgments
patients develop symptoms suggestive of ARIA, including
headache, vomiting and/or nausea, confusion, dizziness, The authors wish to thank Zhang Li and Chu Lei (Biogen
visual impairment, gait difficulties, ataxia, tremor, new- Biotechnology) for their help in the collection and sharing
onset seizures, or significant, and unexpected acute of data.

Volume 1 Issue 1 (2022) 6 https://doi.org/10.36922/an.v1i1.2