Intracranial aneurysms (IA), whether saccular (sIA) or, rarely, fusiform (fIA), can lead to rupture with devastating sequalae. The Kuopio IA Patient and Family Database contains all cases of unruptured sIAs and fIAs, and patients with aneurysmal subarachnoid haemorrhage (aSAH) were admitted to the Kuopio University Hospital from its defined catchment population. Data from several national registries, including the hospital diagnosis registry, medicine reimbursement statistics and the population register have been integrated to the database. The population register has been used to obtain corresponding information on the first-degree relatives of the patients and to create a matched control population to the patients.
The doctoral thesis study by Arttu Kurtelius, BM, had three aims. The first was to determine the prevalence of neurofibromatosis type 1 (NF), a monogenic disorder, in the population-based cohort of IA and aSAH patients, as well as the diagnoses of IA and aSAH in a reverse approach in a nationwide database of NF1 patients. The second aim was to identify families in which parents were concordant for sIA disease, study the propagation of sIA disease to their children, and to study the effect of the familial versus sporadic sIA disease on the sIA risk of the offspring. Thirdly, the study aimed to determine the frequency of abdominal aortic aneurysms (AAA) and thoracic aortic aneurysms (TAA) in sIA and fIA patients and to evaluate a possible genetic connection between fIA and aortic aneurysms.
Only one NF1 patient was identified among the 4,543 IA patients, in line with the prevalence of NF1 in the general population (1/4,500). Three verified IA cases (one unruptured IA and two aSAH cases) were identified in the cohort of 1,410 NF1 patients, with an occurrence of similar magnitude in the control cohort.
A total of 18 couples concordant for the sIA disease with a total of 48 children were identified. Six sporadic-sporadic couples were concordant for subarachnoid haemorrhage (SAH). None of the 24 children to the 12 sporadic-sporadic couples had been diagnosed with SAH or IA disease. Instead, 11 (46%) of the 24 children to the 6 familial-sporadic couples had been diagnosed with SAH or IA disease.
The proportion of fIA diagnosed with AA was 14%. In comparison, 1.2% of sIA patients had a diagnosis of AA. Both fIA and sIA patients had AAs significantly more often than their (1.2% and 0.5%) controls or relatives (0.9% and 0.3%). One likely pathogenic variant in COL5A2 and three variants of unknown significance were identified in MYH11, COL11A1, and FBN1 in four fIA patients.
The results of this doctoral thesis clarify the contested relationship of intracranial aneurysms and NF1, underline the importance of looking at the family history of a patient presenting with an intracranial aneurysm or aneurysmal subarachnoid haemorrhage and provide the impetus to consider screening all patients with fusiform IA for aortic aneurysms.
The doctoral dissertation of Arttu Kurtelius, Bachelor of Medicine, entitled Intracranial Aneurysms: Familial and Hereditary Predisposition in Eastern Finland, will be examined at the Faculty of Health Sciences on 25 January 2020. The Opponent in the public examination will be Professor Nima Etminan of the University of Heidelberg, and the Custos will be Docent Antti Lindgren.
Photo available for download at
https://kuvapankki.uef.fi/A/UEF+kuvahakemisto/18492?encoding=UTF-8
