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Review
Iatrogenic cerebral amyloid angiopathy: an emerging clinical phenomenon
  1. Gargi Banerjee1,
  2. Kiran Samra2,
  3. Matthew E Adams3,
  4. Zane Jaunmuktane4,5,
  5. Adrian Robert Parry-Jones6,7,
  6. Joan Grieve8,
  7. Ahmed K Toma8,
  8. Simon F Farmer9,
  9. Richard Sylvester9,
  10. Henry Houlden5,
  11. Peter Rudge1,
  12. Simon Mead1,
  13. Sebastian Brandner1,2,4,
  14. Jonathan M Schott2,
  15. John Collinge1,
  16. David J Werring10
  1. 1MRC Prion Unit at UCL, Institute of Prion Diseases, London, UK
  2. 2Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
  3. 3Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
  4. 4Division of Neuropathology, National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
  5. 5Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
  6. 6Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
  7. 7Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK
  8. 8Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
  9. 9Department of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
  10. 10Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
  1. Correspondence to Dr Gargi Banerjee, MRC Prion Unit at UCL, Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London W1W 7FF, UK; g.banerjee{at}ucl.ac.uk

Abstract

In the last 6 years, following the first pathological description of presumed amyloid-beta (Aβ) transmission in humans (in 2015) and subsequent experimental confirmation (in 2018), clinical cases of iatrogenic cerebral amyloid angiopathy (CAA)—attributed to the transmission of Aβ seeds—have been increasingly recognised and reported. This newly described form of CAA is associated with early disease onset (typically in the third to fifth decade), and often presents with intracerebral haemorrhage, but also seizures and cognitive impairment. Although assumed to be rare, it is important that clinicians remain vigilant for potential cases, particularly as the optimal management, prognosis, true incidence and public health implications remain unknown. This review summarises our current understanding of the clinical spectrum of iatrogenic CAA and provides a diagnostic framework for clinicians. We provide clinical details for three patients with pathological evidence of iatrogenic CAA and present a summary of the published cases to date (n=20), identified following a systematic review. Our aims are: (1) To describe the clinical features of iatrogenic CAA, highlighting important similarities and differences between iatrogenic and sporadic CAA; and (2) To discuss potential approaches for investigation and diagnosis, including suggested diagnostic criteria for iatrogenic CAA.

  • PRION
  • AMYLOID
  • STROKE

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Footnotes

  • Twitter @jmschott

  • Contributors GB designed and conceptualised study, collected the clinical data, performed the literature searches, and drafted the manuscript. KS collected the clinical data and revised the manuscript for intellectual content. MEA prepared figure 2, and revised the manuscript for intellectual content. ZJ and SB contributed to the neuropathological data, and revised the manuscript for intellectual content. APJ, JG, AKT, SFF, RS, PR and JMS all contributed to the clinical care of the patients described, and revised the manuscript for intellectual content. HH, SM and JC contributed the genetic analyses, and revised the manuscript for intellectual content. DJW contributed to the clinical care of the patients and the design and conceptualisation of the study, and revised the manuscript for intellectual content.

  • Funding GB holds a clinical lectureship funded by Alzheimer’s Research UK (ARUK-CRF2020A-003), the Stroke Association (SA L-MP 20\100002) and the NIHR (no award/grant number). ZJ, AKT, SFF and SB are supported by the UK Department of Health’s NIHR Biomedical Research Centre’s funding scheme to UCLH (no award/grant number). SM and JC are NIHR senior investigators (NF-SI-0617-10175 and NF-SI-0611-10073, respectively). The MRC Prion Unit at UCL is core funded by the UK Medical Research Council (no award/grant number).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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