Ultrastructural connective tissue aberrations in patients with intracranial aneurysms.
OBJECTIVE
An unknown connective tissue defect might predispose for the development and rupture of intracranial aneurysms in some patients. This study of connective tissue samples of a series of patients with intracranial aneurysms investigates the morphology of the extracellular matrix with methods that are currently used in the routine diagnosis of inherited connective tissue disorders.


METHODS
Skin biopsies from 21 patients with intracranial aneurysms, many with multiple aneurysms, were studied by electron microscopy. None of the patients included in this study showed clinical signs of a known connective tissue disorder.


RESULTS
In 7 patients (33%), we observed repetitive aberrations in the morphology of collagen fibrils and elastic fibers of the reticular dermis. The observed ultrastructural findings were somewhat similar to those typically observed in patients with Ehlers-Danlos syndrome (EDS) and in a subgroup of patients with spontaneous cervical artery dissections. The patterns of abnormalities fell into 2 classes: 4 patients displayed abnormalities that resembled those found in patients with EDS type III, and the electron microscopic findings in the skin biopsies from 3 patients resembled those of EDS type IV patients. The sequence of the COL3A1 gene from the patients with EDS type IV-like alterations of the connective tissue morphology was analyzed. No mutation was detected.


CONCLUSIONS
Connective tissue alterations were found in skin biopsies from a minority of patients with intracranial aneurysms. Electron microscopic investigation of skin biopsies from patients and their relatives might become valuable for clinical diagnostics, identification of persons at risk, and basic studies of the pathogenesis of this vascular disease.
Grond-Ginsbach
Caspar
C
Department of Neurology, University of Heidelberg, Heidelberg, Germany. Caspar_Grond-Ginsbach@med.uni-heidelberg.de
Schnippering
Holger
H
Hausser
Ingrid
I
Weber
Ralf
R
Werner
Inge
I
Steiner
Hans H
HH
Lüttgen
Nina
N
Busse
Otto
O
Grau
Armin
A
Brandt
Tobias
T
D000328:Adult; D001706:Biopsy; D003094:Collagen / Q000235:genetics / Q000648:ultrastructure; D024061:Collagen Type III; D003238:Connective Tissue / Q000473:pathology / Q000648:ultrastructure; D003240:Connective Tissue Diseases / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D004547:Elastic Tissue / Q000473:pathology / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000150:complications* / Q000235:genetics; D008297:Male; D008854:Microscopy, Electron; D012867:Skin / Q000473:pathology* / Q000648:ultrastructure
C439971:COL3A1 protein, human; D024061:Collagen Type III; D003094:Collagen