The (Not-So) Curious Case of a Man with Two Brain Aneurysms

Figure 1. Two stable unruptured left middle cerebral artery aneurysms; 5mm (M1, left column) and 7mm (M2, right column); 2007 (top row) and 2019 (bottom row).

This is a case study from the Center for Unruptured Brain Aneurysms (CUBA) of NSPC where several hundred patients with unruptured brain aneurysms are followed in an individualized clinical surveillance and treatment program. White man with polycystic kidney disease, now in his 60s, who was diagnosed with two unruptured brain aneurysms of the left middle cerebral artery (5x5mm and 7x5mm) in 2007 during a routine screening test (Figure 1).

Figure 2. Two unruptured left middle cerebral artery aneurysms (M1, left and M2, right) 12 years after first diagnosis. MRA 3D time-of-flight from 2019.

There was increased risk for occurrence of brain aneurysms due to the presence of polycystic kidney disease. However, the overall risk of aneurysm rupture was assumed to be relatively low. The patient was not a smoker, had no arterial hypertension, and a negative family history for brain aneurysms. He agreed to be included in the individualized unruptured brain aneurysm surveillance and treatment program of NPSC’s Center for Unruptured Brain Aneurysms. In addition, the patient participated in an experimental drug program with daily oral dose of minocycline which was well tolerated.

In 2021, almost fourteen years following the diagnosis of two brain aneurysms, the patient (now in his late 60s) remains asymptomatic with stable anatomy of both middle cerebral artery aneurysms (brain MRA from 2019 shown in Figures 1 and 2; 3D-rendered images from 2010 vs. 2017 in Figure 3). Predicted 5-y risk of rupture is 0.4% (95% CI 0.1-1.5%) per PHASES risk score.

Figure 3. 3D-rendering of patient’s two unruptured middle cerebral artery aneurysms at two different times (courtesy of Dr. MR Ouared). Comparison shows stable anatomy over a 7-year period. Improved anatomic details of rendered models for 2017 due to higher quality of MR source images. ICA (internal carotid artery), MCA (middle cerebral artery), two MCA aneurysms at M1 and M2.

Management Considerations:

Approximately 3% of the US population live with a brain aneurysm (sometimes there are multiple aneurysms) and most of the time, the aneurysm is asymptomatic1. Rarely are people aware that they have a brain aneurysm, and the first diagnosis is often made following brain imaging obtained for unrelated reasons or from screening. The annual incidence of aneurysmal subarachnoid hemorrhage is 30,000 in the US. Although a devastating type of intracranial hemorrhage and the most feared outcome in patients with unruptured brain aneurysms, it is very likely that most patients will live a life uninterrupted by symptoms caused by the brain aneurysm.

Statistics aside, on an individual patient level, the best course of action for the majority of patients with unruptured brain aneurysms is observation with routine clinical and imaging follow-up. The risk of rupture of brain aneurysms varies widely depending on numerous clinical and anatomic factors. Understanding the true risk of rupture (and the risk of treatment procedures) is important to devise the best management plan (observation, interventional or surgical treatment) for individuals living with brain aneurysms². Some risk factors of rupture are known and commonly accepted (e.g. size, location, smoking, arterial hypertension, family history). However, exactly how much these risk factors account for the overall risk and which other yet unknown factors may influence the future outcome are part of the ongoing research and still left to be determined.

Systematic clinical observation of unruptured brain aneurysms over a long period, as attempted with the individualized surveillance and treatment program provided by the Center for Unruptured Brain Aneurysms, helps to identify and determine risk factors of rupture which are parts of the puzzle to better understanding the natural history of unruptured brain aneurysms. Minocycline, a tetracycline derivative antibiotic, has anti-inflammatory and metalloproteinase-inhibitory properties, and has shown to have aneurysm wall stabilizing effects in animal models³.

References:

1. Thompson BG, Brown RD, Amin-Hanjani S, et al. Guidelines for the management of patients with unruptured intracranial aneurysms. AHA/ASA Guideline. Stroke 2015; 46: 2368-2400. https://pubmed.ncbi.nlm.nih.gov/26089327/
2. Greving JP, Wermer MJH, Brown RD et al. Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol 2014; 13: 59-66. https://www.sciencedirect.com/science/article/abs/pii/S1474442213702631
3. Makino H, Tada Y, Wada K, et al. Pharmacological stabilization of intracranial aneurysms in mice – a feasibility study. Stroke 2012; 43: 2450-6 https://pubmed.ncbi.nlm.nih.gov/22798328/