Transient Focal Neurological Events in Cerebral Amyloid Angiopathy and the Long-term Risk of Intracerebral Hemorrhage and Death: A Systematic Review and Meta-analysis

JAMA Neurol. 2022 Jan 1;79(1):38-47. doi: 10.1001/jamaneurol.2021.3989.


Importance: Transient focal neurological episodes (TFNEs) are a frequently overlooked presentation of cerebral amyloid angiopathy (CAA), a condition with prognostic implications that are still not well described.

Objective: To perform a systematic review and meta-analysis to examine the factors associated with incident lobar intracerebral hemorrhage (ICH) and death in patients with CAA presenting with TFNEs.

Data sources: A systematic review and individual participant meta-analysis including (1) a hospital-based cohort and (2) the results obtained from a systematic search performed in MEDLINE and Embase completed in December 2019.

Study selection: Included studies were observational reports of TFNEs. Patient-level clinical, imaging, and prognostic data were required for inclusion. For aggregate data studies, patient-level data were requested. Disagreements were resolved by consensus.

Data extraction and synthesis: Data were extracted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines by 4 independent reviewers. The quality of reports was determined based on the modified Pearson Case Report Quality Scale.

Main outcomes and measures: The clinical characteristics of TFNEs, neuroimaging features, and use of antithrombotics during follow-up were considered exposures. The predefined main outcomes were lobar ICH and risk of death during follow-up.

Results: Forty-two studies and 222 CAA-associated TFNE cases were included from the initial 1612 records produced by the systematic search; 26 additional patients (11 men [42.3%]; mean [SD] age, 77 [8] years) were provided by the hospital-based cohort. A total of 108 TFNEs (43.5%) consisted of motor symptoms. Convexity subarachnoid hemorrhage and cortical superficial siderosis were detected in 193 individuals (77.8%) and 156 individuals (62.9%) in the systematic search and hospital-based cohort, respectively. Follow-up duration could be obtained in 185 patients (median duration, 1 year [IQR, 0.8-2.5 years]). During follow-up, symptomatic lobar ICH occurred in 76 patients (39.4%). Motor symptoms (odds ratio, 2.08 [95% CI, 1.16-3.70]) at baseline and antithrombotic use during follow-up (odds ratio, 3.61 [95% CI, 1.67-7.84]) were associated with an increase in risk of lobar ICH. A total of 31 patients (16.5%) died during follow-up; lobar ICH during follow-up and cortical superficial siderosis were the main risk factors for death (odds ratio, 3.01 [95% CI, 1.36-6.69]; odds ratio, 3.20 [95% CI, 1.16-8.91], respectively).

Conclusions and relevance: Patients presenting with CAA-associated TFNEs are at high risk of lobar ICH and death. Motor TFNEs and use of antithrombotics after a TFNE, in many cases because of misdiagnosis, are risk factors for ICH, and therefore accurate diagnosis and distinguishing this condition from transient ischemic attacks is critical.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cerebral Amyloid Angiopathy / complications
  • Cerebral Amyloid Angiopathy / epidemiology*
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / epidemiology*
  • Cohort Studies
  • Humans
  • Ischemic Attack, Transient / complications
  • Ischemic Attack, Transient / epidemiology*
  • Risk Factors