Early Identification of Intracranial Aneurysms in Pediatric Patients with Tuberous Sclerosis: A New Challenge for the Future?

Introduction: Tuberous sclerosis complex (TSC) is a rare autosomal-dominant inherited disease. Arterial wall developmental disorders, such as aneurysms, in association with TSC have been well described for extracranial vasculature. Whereas, intracranial aneurysms (IAs) have not previously been addressed in the literature. A systematic review was performed to assess demographic, radiologic and clinical features of IA in TSC Patients.

Material and Methods: A comprehensive literature search of 3 databases (PubMed, Scopus and Web of Science) was performed by the first author (M.C.) in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In addition, we screened our observational database containing records of all consecutive patients with IAs treated at our institution since 2003, which yielded 2 additional cases of IA associated with TSC, and these cases were included in our analysis. In both cases, patient informed consent was obtained. All analyses were performed using IBM SPSS Statistics version 25 for Windows. Due to a lack of accurate and completed numerical information, we mainly conducted descriptive analysis.

Results: Thirty-three TSC patients with a total of 42 IAs were included in this review. Three individuals (adults) presented with subarachnoid hemorrhage (SAH). Among the collected series, there was a higher prevalence of pediatric cases (n =  22, 66.7%), 8 of them were 2 years old or younger. In this pediatric population, IAs were all unruptured, large/giant in 72.7%, fusiform in 59.1%, multiple in 27,2% and originated from the internal carotid artery in 63.6% of the cases. Also, they were diagnosed whether incidentally (n = 10, 45.4%) or due to a new-onset of a neurological deficit (n = 6, 27.2%), mostly with a large/giant IA-size (respectively: n = 6, n = 4). Moreover, a rapid aneurysmal growth was described in two pediatric patients; in our case, a 14-month-old male and in another case of the literature, a 13-month-old female.

Discussion: TSC patients with IAs are characterized with a higher proportion of large/giant, fusiform IAs and young age, suggesting a rapid aneurysmal growth. Furthermore, most of the aneurysms were asymptomatic and large/giant at the time of the diagnostic. In the last recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference, the coexistence of IAs with TSC was not mentioned, although 3 cases of SAH in association with TSC were reported. In this conference, magnetic resonance imaging (MRI) was recommended at diagnosis of TSC and every 1 to 3 years until the age of 25 years to screen for development of subependymal giant cell tumors. Therefore, an enhancement of the regular MRI screenings with a cranial time-of-flight magnetic resonance angiography (TOF-MRA) might be reasonable in pediatric TSC patients for an early diagnostic of IAs and a timely identification of aneurysmal growth.

Conclusion: An early diagnostic of asymptomatic IAs and a prompt identification of aneurysmal growth is a real challenge for TSC patients. Therefore, we recommend enhancing the regular MRI screenings −every 1 to 3 years− with a TOF-MRA. Additionally, large population-based patient registers are required to improve the understanding of the epidemiology and pathogenesis of IA formation in patients with TSC.

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