Subarachnoid Hemorrhage Secondary to Aneurysm Rupture in a Patient with Osteogenesis Imperfecta with COL1A1 Mutation

Sir, Osteogenesis imperfecta (OI) is a disorder of bone fragility chiefly caused by mutations in the COL1A1 and COL1A2 genes that encode type I procollagen. Patients with OI show a wide range of clinical symptoms from asymptomatic, to individuals leading a normal life, to being severe enough, resulting in perinatal death. It has been reported that the collagen type 1 alpha-2 gene (COL1A2) mutation may predispose patients to intracranial aneurysms (IAs), and that the cerebrovascular system is less frequently involved in OI due to other mutations. We report the case of a patient with OI with COL1A1 mutation with SAH due to IAs. A 66-year-old female patient, known case of OI and hypertension, presented with complaints of severe headache and vertigo along with slurring of speech and transient weakness in the right half of body. She had no family history of any cerebrovascular malformation. Neurologic examination revealed slight disturbance in sensorium (Glasgow Coma Scale score, 14) and neck stiffness without any focal deficit. On general examination, she had blue sclera, hypertension, and had sustained repeated fractures of the extremities in her childhood. Her height was 150 cm (equal to the average height of Indian women) with no major skeletal deformities. The patient’s son also had blue sclera and a history of multiple fractures; however, there was no history of bone fragility in her parents, and other siblings. According to these findings, the diagnosis of OI was made during admission. Patient was admitted in ICU and noncontrast computed tomography The brain was done which revealed subarachnoid hemorrhage (SAH) on the right side and in bilateral basal cistern with age-related generalized cerebral atrophy with chronic ischemic demyelination changes. CT Angiography brain was done which was suggestive of right middle cerebral artery bifurcation and anterior communicating artery aneurysm [Figure 1]. She thereafter underwent right pterional craniotomy and aneurysm clipping. Intraoperatively, there was no aneurysmal rupture or any vascular fragility noted, both the aneurysms were clipped [Figure 2]. The surgery was uneventful. No significant difference was noted in the background of connective tissue disorder. Postoperatively, her condition gradually improved and at the time of discharge she was conscious, alert, moving all four limbs and hemodynamically stable. Genetic analysis of the patient was done where she was tested for mutations in the genes responsible for OI (COL1A1, COL1A2, CRTAP, P3H1) using Next Generation Sequencing supported by Sanger sequencing. The result was that patient was heterozygous for W1275*:c; 3824G > A mutation in COL1A1 gene.Figure 1: (a) NCCT head showing SAH with CT angiography reconstruction showing right middle cerebral artery and anterior communicating artery aneurysm. (b) CT angiography brain showing right middle cerebral artery and anterior communicating artery aneurysmFigure 2: Intraoperative images of clipped aneurysmsThe diagnosis of OI is based on clinical signs, symptoms, and positive family history. Most patients with OI have a mutation of either the COL1A1 or COL1A2 gene, which are the two genes that code for alpha-1 and alpha-2 chains of type 1 collagen, respectively. Type 1 collagen is the most abundant connective tissue in the vertebrate and is found in other tissues, including blood vessels. Interstitial type 1 collagen was reported to be deposited on the surfaces of smooth muscle cells or along elastin filaments in the cerebrovascular wall, and thus, type 1 collagen might play a role in the rigidity and elasticity of the vascular wall. In patients with OI COL1A2, mutations have known association with intracranial aneurysmal rupture and SAH. However in our case, we found an uncommon association of mutation in COL1A1 gene. Association with such genetic mutations are rare and not quite reported in literature, only one case mentions its association.[1] The published literature does not show any evidence of increased risk of intraoperative aneurysmal rupture or any complication in the background of OI. The difference, however, is seen in association with multiple aneurysms,[2] which should be screened for, and wound healing, which is found to be slow in patients with connective tissue disorders. There are a few case reports where patients having SAH due to aneurysm rupture has been described in patients with OI. The treatment modality chosen included both clipping and coiling. The preference of treatment option was based on aneurysm location, characteristics, patient factors, and surgeon’s choice; same as in our case. Most of the vascular complications in patients with OI have been reported as artery dissections in the literature. A few sporadic case reports described intracranial artery dissections complicated by OI with COL1A2 gene are observed but none with COL1A1 gene mutations only one case has been reported yet.[1] To our knowledge, SAH secondary to ruptured IA in patients with OI has been reported in only nine cases that too with COL1A2 mutations [Table 1]. It is difficult to determine whether ruptured IAs are truly caused by OI or accidentally complicated by OI.Table 1: Case reports of subarachnoid hemorrhage secondary to ruptured intracranial aneurysm with osteogenesis imperfectWe here describe a unique case of SAH secondary to ruptured saccular IA in a middle-aged female patient with clinically diagnosed OI with COL1A1 mutation. Mutation in the COL1A1 gene is a rare finding, which makes this case unique. There may be some causative relationship between OI and SAH because there are several reported cases of SAH secondary to cerebral aneurysm in patients with OI with COL1A2 mutation and not COL1A1 mutation. Caution should be borne in mind while managing such patients with appropriate screening and prognostication. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.