Risk factors for lobar intracerebral hemorrhage and death in cerebral amyloid angiopathy

Patients with cerebral amyloid angiopathy (CAA)-associated transient focal neurological episodes (TFNEs) have been found to be at increased risk of lobar intracerebral hemorrhage (ICH) and death. These results were published in JAMA Neurology.

TFNEs have been increasingly associated with CAA. These patients have stereotyped, recurrent, short-lived focal somatosensory or motor disorders lasting 10-30 minutes. However, TFNEs can also mimic other neurological disorders such as transient ischemic attacks, focal seizures, and migraine auras. To fill the potential knowledge gap about TFNE properties and the potential impact on CAA prognosis, researchers from Hospital del Mar in Spain conducted a review of patient records in two Spanish hospitals, as well as a systematic review and meta-analysis.

Patients (N=26) diagnosed with CAA with TFNE or amyloid flares between 2010 and 2020 were evaluated for symptoms and outcome. Researchers also searched publication databases for studies on CAA in combination with TFNEs up to December 2019.

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Using hospital records, patients had probable (n=15) or possible (n=11) CAA, 42% were male and had a mean age of 77 years (SD [SD], 8 years. Patients had motor TFNEs (n=15), sensory TFNEs with negative motor symptoms (n=9), and sensory-only TFNEs (n=6). Few patients developed isolated aphasia (n=1), aphasia and visual symptoms (n=1), and isolated visual symptoms (n=1).

During imaging assessment, 85% had TFNE with convex subarachnoid hemorrhage (CSAH), cortical superficial siderosis (CSS; 54%), and lobar microhemorrhages (54%).

Almost a third of patients (31%) were receiving antithrombotic therapy when they presented with the first TFNE, and 12 patients were receiving antithrombotic therapy during follow-up.

At a median follow-up of 1.63 years, eight patients had acute symptomatic lobar ICH and three patients died.

A total of 48 studies with 222 patients were included in the meta-analysis. This patient population consisted of 57% males with a mean age of 74 (SD, 7) years.

The hospital and meta-analysis cohorts differed significantly in diabetes rate (23% vs. 5%; p=0.03) and follow-up time (mean 1.64 vs. 0.82; p=0.001), respectively.

The pooled dataset included three definitive CAAs, seven probable CAAs with pathology, 96 probable CAAs, and 142 possible CAAs. Almost half of the TFNEs had motor symptoms (43.5%) and most (85.5%) had CSAH or CSS. Symptomatic lobar ICH occurred in 39.4% and 16.5% died.

Risk of ICH associated with antithrombotic use (odds ratio [OR], 1.99; 95% CI, 1.07-3.7) and CSAH (OR, 0.39; 95% CI, 0.2-0.79).

Mortality was associated with acute ischemic stroke with CSS (OR 27.95; 95% CI 3.60-217.40), lobar ICH (OR 4.46; 95% CI 1.78-11.159), and CSS alone (OR 4.45, 95% CI, 1.78-11.16).

This study was limited by the quality of the data in the meta-analysis, which included high heterogeneity.

“Motor TFNEs and post-TFNE use of antithrombotics, in many cases due to misdiagnosis, are risk factors for ICH, and therefore accurate diagnosis and differentiation of this condition from transient ischemic attacks is crucial,” the researchers concluded.

These data suggested that motor TFNE and antithrombotic treatment were potential risk factors for lobar ICH in patients with CAA, likely increasing the risk of mortality. Further studies are needed to better stratify patients with CAA-associated TFNEs for bleeding risk.

Disclosure: One author stated industry affiliations. For a full list of disclosures, see the original article.


Sanchez-Caro JM, de Ubago IdLM, Ruiz EdC, et al. Transient focal neurologic events in cerebral amyloid angiopathy and the long-term risk of intracerebral hemorrhage and death: A systematic review and meta-analysis. JAMA Neurol. Published online November 15, 2021. doi:10.1001/jamaneurol.2021.3989

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