Connective Tissue Abnormalities in Patients with Ruptured Intracranial Aneurysms and No Known Systemic Connective Tissue Disorder

Abstract

Background: Defect in internal elastic lamina, defect in tunica media, and the amount of collagen and elastin play a role in vessel wall weakening leading to aneurysm formation. A similar picture may be found in connective tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome (EDS), neurofibromatosis type 1, and Loeys-Dietz syndrome (LDS), where there is a predominant disorder of collagen formation/maturation.

Methods: Histopathology of skin and the superficial temporal artery (STA) was done. All specimens were obtained during craniotomy for ruptured aneurysm clipping or other indicated procedures (for control subjects). Parameters in skin biopsy seen were epithelial thickness, dermal collagen thickness, and so forth. For the STA, parameters such as intimal thickness, intimal proliferation, thickness of media, and so forth were studied.

Results: Twenty cases and twenty control subjects were studied. The mean age of the study population was 40.5 years. Salient findings on skin biopsy in patients of intracranial aneurysms (IAs) (cases) were haphazard orientation of collagen, inflammation in the subepidermal layer, increased dermal collagen thickness, and reduced and/or fragmented elastic fibers. Prominent findings on vessel wall biopsy were intimal proliferation, reduplication of internal elastic lamina, reduced and/or fragmented elastin, and vacuolation of smooth muscle cells. The average number of aberrations per patient was significantly higher in cases than control subjects.

Conclusions: The histologic changes seen in skin and the STA in cases of IAs signify a weak connective tissue. Some of these findings are also seen in known connective tissue disorders such as Marfan syndrome, EDS, neurofibromatosis type 1, and LDS. The connective tissue abnormalities found in patients with IAs may be congenital, which gets further accentuated by known risk factors leading to weak vessel wall and subsequent aneurysm formation.

Keywords: Connective tissue disorders; Ehlers-Danlos syndrome; Internal elastic lamina; Intracranial aneurysms; Marfan syndrome; Media.