Autosomal dominant inheritance of a predisposition to thoracic aortic aneurysms and dissections and intracranial saccular aneurysms.

A genetic predisposition for thoracic aortic aneurysms and dissections (TAAD) can be inherited in an autosomal dominant manner with decreased penetrance and variable expression. Four genes identified to date for familial TAAD account for approximately 20% of the heritable predisposition. In a cohort of 514 families with two or more members with presumed autosomal dominant TAAD, 48 (9.3%) families have one or more members who were at 50% risk to inherit the presumptive gene causing TAAD had an intracranial vascular event. In these families, gender is significantly associated with disease presentation (P < 0.001), with intracranial events being more common in women (65.4%) while TAAD events occurred more in men (64.2%,). Twenty-nine of these families had intracranial aneurysms (ICA) that could not be designated as saccular or fusiform due to incomplete data. TGFBR1, TGFBR2, and ACTA2 mutations were found in 4 families with TAAD and predominantly fusiform ICAs. In 15 families, of which 14 tested negative for 3 known TAAD genes, 17 family members who were at risk for inheriting TAAD had saccular ICAs. In 2 families, women who harbored the genetic mutation causing TAAD had ICAs. In 2 additional families, intracranial, thoracic and abdominal aortic aneurysms were observed. This study documents the autosomal dominant inheritance of TAADs with saccular ICAs, a previously recognized association that has not been adequately characterized as heritable. In these families, routine cerebral and aortic imaging for at risk members could prevent cerebral hemorrhages and aortic dissections.

Vestibular tributaries to the vein of the vestibular aqueduct.

CONCLUSION: The vein of the vestibular aqueduct drains blood from areas extensively lined by vestibular dark cells (VDCs). A possible involvement in the pathogenesis of an impaired endolymphatic homeostasis can be envisioned at the level of the dark cells area. OBJECTIVES: The aim of this study was to investigate the vascular relationship between the vein of the vestibular aqueduct and the vestibular apparatus, with focus on the VDCs. METHODS: Sixteen male Wistar rats were divided into groups of 6 and 10. In the first group, 2 µm thick sections including the vein of the vestibular aqueduct, utricle, and crista ampullaris of the lateral ampulla were examined by light microscopy and computer-generated three-dimensional imaging. In the second group, ultrathin sections including venules and VDCs were examined by transmission electron microscopy. RESULTS: A microvascular network was observed in close relation to the VDCs in the utricle and the crista ampullaris of the lateral semicircular canal in the vestibular apparatus. One major vein emanated from these networks, which emptied into the vein of the vestibular aqueduct. Veins draining the saccule and the common crus of the superior and posterior semicircular canals were likewise observed to merge with the vein of the vestibular aqueduct.

Age-related blood flow and capillary changes in the rat utricular macula: a quantitative stereological and microsphere study.

Vascular change may contribute to age-related vestibular dysfunction. Previously, we reported a significant age-related decrease in blood flow (BF) and mean capillary diameter (D(cap)) in the rat posterior canal crista. The purpose of this study was to examine an otolith organ, the utricle, for similar changes. Old male Fischer 344 rats (O; 28-31 mos) were anesthetized, and the left cardiac ventricle was transcutaneously injected with radioactive microspheres to determine BF. The temporal bones were removed, fixed, and decalcified. The utricles were dissected free and placed into a gamma counter with the reference samples. The specimens were then plastic embedded and serially sectioned at 1 microm according to the vertical section technique. Microsphere surface counts were made and neuroepithelial BF calculated. A systematic random set of sections was sampled and analyzed using stereological techniques for estimates of D(cap), capillary surface area/unit volume (S(v,cap)), capillary length/ unit volume (L(v,cap)), and volume of utricular neuroepithelium (V(ut)). Using these data, total capillary surface (S(cap)) and total length (L(cap)) were calculated. Statistical comparisons were made with data from our previous study of young animals (Y; 3-6 mos). Results indicate a significant age-related decrease in BF (Y = 0.125 microL/min, O = 0.062 microL/min; P = 0.003), D(cap) (Y = 5.95 micro, O = 4.57 microm; P = 0.0002), S(vcap) (Y = 12.33 mm2/mm3, = 9.87 mm2/mm3, P = 0.016), S(cap) (Y = 0.178 mm2, O = 0.129 mm2; p = 0.01), and V(ut) (Y = 0.014 mm3, O = 0.013 mm3; P = 0.04) with no significant change in L(v,cap) (Y = 655 mm/mm3, O = 686 mm/mm3, P = 0.41) or L(cap) (Y = 9.47 mm, O = 8.96 mm; P = 0.49). These age-related vascular changes are likely to have a significant impact on utricular physiological and thus, dysequilibrium.

Saccular cerebral aneurysms in young adults.

BACKGROUND: The formation and rupture of cerebral aneurysms has been controversial. In order to clarify their nature, this study investigates the size and location of ruptured and unruptured aneurysms in young adults and the results of surgery. METHODS: The subjects of this study are 35 patients with ruptured and two with unruptured aneurysms. They range in age from 20 to 39 years. The size and location of their aneurysms were determined by angiographic measure of their maximal inner diameters. Direct surgery was performed on 34 patients with ruptured aneurysms and on one with an unruptured aneurysm. RESULTS: Ruptured aneurysms in young adults increase in number and size as they grow older. In young adults showing no atherosclerosis or hypertension, ruptured aneurysms occurred in locations and with a frequency found in patients with hypertension. In young adults, aneurysms in the internal carotid artery larger than 3.5 mm (Fisher's exact test; p < 0.05) and the anterior communicating artery showed a tendency to rupture. The surgery produced excellent results in young adults with grade I to III by Hunt and Kosnik classification, but extremely poor results for those with grade IV resulting from vasospasm (Fisher's exact test; p < 0.05). CONCLUSION: It is possible that aneurysms found in young adults might in fact have been present from childhood and adolescence, increasing sufficiently in size to rupture in the forties and fifties. Accordingly, while aneurysm formation may be related to fragile arterial walls, aneurysm rupture may be the result of aging factors such as hypertension and atherosclerosis. Even in young adults, vasospasm had an impact on the outcome of surgery.

Vascular patterns of the saccule of the rat: a microcorrosion cast study.

A scanning electron microscope study of corrosion cast preparations of the vessels of the saccule was carried out in adult rats. This method shows the microvasculature of the saccule in the three-dimensional model. As a result of this technique we have been able to demonstrate a particular microvasculature of the saccule in the rat's inner ear. The main blood supply of the saccule consists of the arterioles coming from the vestibulocochlear artery entering the anterior margin of the macula sacculi. A few branches of the anterior vestibular artery enter the macula sacculi from the superior margin. The saccular vein drains the venous blood from a dense capillary area underneath the striola to the posterior vestibular vein which eventually ends in the vein of the cochlear aqueduct.

Effect of intermittent blood pressure elevation on the growth of experimental saccular aneurysms in the rat.

In this study we applied the technique described in the previous paper (see pp. 103-106 of previous issue (1991); 13(2)) to rats with experimental saccular aneurysms. We found that the mean sizes and some growth ratios of experimental aneurysms were significantly larger in the intermittent blood pressure elevation groups than in the control groups. The increase of growth ratios was proportional to the number of transient blood pressure elevations. The morphological structure of these saccular aneurysms showed that the regenerative processes in the aneurysm wall had obviously been interfered with in animals with intermittent blood pressure elevation. The effective mechanism of this influential factor is discussed.

Morphological study of blood-labyrinth barrier in the vestibular organs under normal and experimental acute hypertensive and acute hypotensive conditions.

In order to examine a blood-labyrinth barrier in the vestibular region, capillary permeability of the vestibular organs, i.e. the sacculus, the utriculus and the ampullae of semicircular canals, were studied light and electron microscopically by the horseradish peroxidase (HRP) tracer method. Intravenously infused HRP was not observed outside capillaries because of the tightness of endothelial tight junctions and the paucity of pinocytotic vesicles. Furthermore, the effect of drug-induced acute hypertension and acute hypotension on the capillaries of the vestibular organs was studied morphologically using the tracer technique. In each experiment, there was no extravasation of HRP from capillaries, thus agreeing with the results of the experiment made under normal conditions. These findings mean that capillaries of the vestibular region are of ordinary brain capillary type and contribute to the blood-labyrinth barrier to macromolecules such as HRP both under normal conditions and following abrupt changes in blood pressure.

Morphological evidence of vestibular pathology in long-term experimental diabetes mellitus. I. Microvascular changes.

The influence of long-term experimental diabetes on the microvasculature of the saccule and utricle was investigated using quantitative light and electron microscopic techniques. Basal lamina thickening or reduplication, typically seen in diabetic microangiopathy, were not observed. However, morphometric analysis did reveal a statistically significant increase in capillary diameters along with an increased vascularization of both the saccule and utricle. Both of these microvascular abnormalities may have been caused by the hemodynamic alterations known to occur in diabetes. These alterations include decreased deformability of red blood cells and increased blood viscosity. Either of these factors can lead to a greater stress on the capillary wall and possibly to a reduced oxygen delivery to the tissues.

Basal lamina pathology of the utricle and endolymphatic duct in Ménière's disease.

Labyrinthectomy was performed in a patient with a 4-year history of Ménière's disease. The utricle and the proximal portion of the endolymphatic duct were studied using light and electron microscopy. The epithelium varied in height from squamous to columnar. The basal lamina lining the columnar epithelial cells showed marked thickening which was visible in the light microscope. Electron microscopy revealed that the basal lamina had a fibrillar structure. The basal lamina of adjacent blood vessels also showed pathologic thickening with similar fibrillar texture. The significance of basal lamina thickening in association with Ménière's disease is discussed.

Vein of the vestibular aqueduct.

The vein of the vestibular aqueduct (VVA) was investigated in a series of 40 human temporal bones. The processing included vascular injection with a colored medium, decalcification and cutting in serial, thick sections, which were put in a clear fluid and studied with a stereo-microscope. The labyrinthine roots of the VVA are the single veins of the ampulla and simple limbs of the semicircular canals and of the posterior wall of the utricle. They drain the rich capillary bed of the simple endolymphatic walls of the canals and the utricle, as well as a small peripheral area of the cristae and the utricular macula. The VVA leaves the vestibule through an individual bone canal running parallel to the vestibular aqueduct up to the dura of the posterior side of the petrosa in the area of the endolymphatic sac. It then opens in the inferior petrosal sinus or the jugular bulb. The vein receives other branches from the bone, dura and sac. Correct information on the course of this vein appears to be lacking in contemporary textbooks and articles, although it has been correctly described since the last century.