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Fatal Iatrogenic Cerebral Amyloid-Related Encephalitis in a patient treated with lecanemab for Alzheimer’s disease: neuroimaging and neuropathology
Schrag M, Solopova E, Romero-Fernandez W, Harmsen H, Antunes LV, Wang E, Maldonado J, Shostak A et al.. Research Square, 2023-05-10
Topic: Amyloid, tau and blood-test diagnosis
Abstract We report the case of a 79-year-old woman in good general health aside from early-stage Alzheimer’s disease who was enrolled in a randomized controlled trial of the novel therapeutic monoclonal antibody lecanemab where she was treated with the placebo, and subsequently in the open label extension study where she received lecanemab infusions every two weeks. After the third infusion, she suffered a seizure followed by aphasia and progressively worsening encephalopathy. Magnetic resonance imaging revealed multifocal cerebral edema and an increased burden of cerebral microhemorrhages compared to pre-trial imaging, consistent with Amyloid Related Imaging Abnormality (ARIA). She was treated with an antiepileptic regimen and high-dose intravenous corticosteroids but continued to worsen and expired after five days in the hospital. The family requested an autopsy and consented to evaluation of her brain for research. Post-mortem MRI confirmed extensive microhemorrhagic changes in the temporal, parietal and occipital lobes, some of which were visible on gross inspection of the brain. Autopsy confirmed APOE genotype of E4/E4 and the presence of typical neuropathological features of Alzheimer’s disease along with severe cerebral amyloid angiopathy with inflammatory features, including perivascular lymphocytic infiltrates, reactive macrophages and fibrinoid degeneration of vessel walls. There were deposits of β-amyloid in meningeal vessels and penetrating arterioles with numerous microaneurysms. Cerebral microhemorrhages were associated with arterioles harboring β-amyloid deposits and having degenerative morphologies. We conclude from these results that the patient likely died as a result of severe cerebral amyloid angiopathy with marked microvascular degeneration and meningoencephalitis. Further study of the mechanism of ARIA and the neuropathological changes associated with plaque clearance are needed.
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APA 7th
Schrag, M., Solopova, E., Romero-Fernandez, W., Harmsen, H., Antunes, L. V., Wang, E., et al. (2023). Fatal Iatrogenic Cerebral Amyloid-Related Encephalitis in a patient treated with lecanemab for Alzheimer’s disease: neuroimaging and neuropathology. Research Square. https://doi.org/10.21203/rs.3.rs-2865642/v1
Vancouver
Schrag M, Solopova E, Romero-Fernandez W, Harmsen H, Antunes LV, Wang E, et al. Fatal Iatrogenic Cerebral Amyloid-Related Encephalitis in a patient treated with lecanemab for Alzheimer’s disease: neuroimaging and neuropathology. Research Square. 2023. doi:10.21203/rs.3.rs-2865642/v1.
BibTeX
@article{schrag2023-2f35ceff,
author = {Schrag, M. and Solopova, E. and Romero-Fernandez, W. and Harmsen, H. and Antunes, L. V. and Wang, E. and Maldonado, J. and Shostak, A. and others},
title = {{Fatal Iatrogenic Cerebral Amyloid-Related Encephalitis in a patient treated with lecanemab for Alzheimer’s disease: neuroimaging and neuropathology}},
journal = {Research Square},
year = {2023},
doi = {10.21203/rs.3.rs-2865642/v1},
url = {https://doi.org/10.21203/rs.3.rs-2865642/v1}
}
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Key findings
- Magnetic resonance imaging revealed multifocal cerebral edema and an increased burden of cerebral microhemorrhages compared to pre-trial imaging, consistent with Amyloid Related Imaging Abnormality (ARIA).
- Cerebral microhemorrhages were associated with arterioles harboring β-amyloid deposits and having degenerative morphologies.
- We conclude from these results that the patient likely died as a result of severe cerebral amyloid angiopathy with marked microvascular degeneration and meningoencephalitis.
- Further study of the mechanism of ARIA and the neuropathological changes associated with plaque clearance are needed.
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Study details
- Study designrandomized controlled trial
- Evidence strengthHigh
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 44 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for sample size, effect reported and studied in people because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 27 of the 62 points we could judge it on, which is 44 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 27 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 27 of the 62 points we could judge it on is 44 out of 100. |
| Total | 44 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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