Risk Factors for Lobar Intracerebral Hemorrhage and Death in Cerebral Amyloid Angiopathy

subarachnoid hemorrhage
subarachnoid hemorrhage
In a systematic review and meta-analysis, researchers examined the potential risk factors associated with incident lobar intracerebral hemorrhage and death in patients with CAA presenting with TFNEs.

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

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

Patients (N=26) who had a diagnosis of CAA with either TFNE or amyloid spells between 2010 and 2020 were assessed for symptoms and outcomes. The researchers also searched publication databases through December 2019 for studies of CAA combined with TFNEs.

Using hospital records, patients had probable (n=15) or possible (n=11) CAA, 42% were men, and were aged mean 77 (standard deviation [SD], 8) years. Patients exhibited motor TFNEs (n=15), sensory TFNEs with negative motor symptoms (n=9), and purely sensory TFNEs (n=6). Few patients developed isolated aphasia (n=1), aphasia and visual symptoms (n=1), and isolated visual symptoms (n=1).

During neuroimaging assessment, 85% had TFNE with convexity subarachnoid hemorrhage (CSAH), cortical superficial siderosis (CSS; 54%), and lobar microbleeds (54%).

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

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

In the meta-analysis, a total of 48 studies comprising 222 patients were included. This patient population was 57% men aged mean 74 (SD, 7) years.

The hospital-based and meta-analysis cohorts differed significantly for the rate of diabetes (23% vs 5%; P =.03) and follow-up time (mean, 1.64 vs 0.82; P =.001), respectively.

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

Risk for 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 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,” the researchers concluded.

These data indicated that motor TFNEs and antithrombotic treatment were potential risk factors for lobar ICH among patients with CAA, which likely increased mortality risk. More study is needed such that patients with CAA-associated TFNEs may be better stratified for hemorrhage risk.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Sanchez-Caro JM, de Ubago IdLM, Ruiz EdC, et al. 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. Published online November 15, 2021. doi:10.1001/jamaneurol.2021.3989