The familial occurrence of intracranial aneurysms.
01 Mar 1970-Neurology (Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology)-Vol. 20, Iss: 3, pp 283-283
TL;DR: Three examples show that intracranial saccular aneurysms are a heterogeneous disorder; i.e., the same clinical and pathological syndrome is produced by more than one cause.
Abstract: INTRACRANIAL saccular aneurysms are usually regarded as congenital in origin but their etiology is unknown. Any clue that might lead to better understanding of their pathogenesis is worth pursuit, and one such clue is their familial occurrence. One of us has recently reported 3 families, each with 2 affected individuals.lP2 We have subsequently studied these families in greater detail and the results are reported here. We have also reviewed other familial cases previously published and personally communicated to us. In addition, we have attempted to collect information on variations in incidence of intracranial aneurysm in different countries and ethnic groups. While the role of genetic factors in most cases of intracranial aneurysm is unknown, aneurysms occasionally may be due to the inheritance of a single mutant gene, such as those occurring as a complication of the dominantly inherited disorders of connective tissue (for instance, the Ehlers-Danlos ~yndrome,~.3,* which is reported in the first pedigree set out here) or in association with polycystic kidneys.5.6 These examples show that intracranial saccular aneurysms are a heterogeneous disorder; i.e., the same clinical and pathological syndrome is produced by more than one cause. We have attempted to discern whether other familial cases could be separated from the larger group.
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TL;DR: The incidence of subarachnoid haemorrhage (SAH) is 6-8 per 100 000 person years, peaking in the sixth decade, and the morbidity and mortality for elective surgical treatment of unruptured aneurysms is high.
Abstract: The incidence of subarachnoid haemorrhage (SAH) is 6-8 per 100 000 person years, peaking in the sixth decade. SAH, mostly due to rupture of an intracranial aneurysm, accounts for a quarter of cerebrovascular deaths. Aneurysms increase in frequency with age beyond the third decade, are 1.6 times more common in women and are associated with a number of genetic conditions. Prospective autopsy and angiographic studies indicate that between 3.6 and 6% of the population harbour an intracranial aneurysm. Studies have found an increased rate of SAH in first degree relatives of SAH patients (relative risk 3.7-6.6). In affected families, the most frequent relationship between sufferers is sibling to sibling. The rupture rate of asymptomatic aneurysms was thought to be 1-2% per annum, but the recent International Study of Unruptured Intracranial Aneurysms found that the rupture rate of small aneurysms was only 0.05% per annum in patients with no prior SAH, and 0.5% per annum for large (>10 mm diameter) aneurysms and for all aneurysms in patients with previous SAH. Non-invasive tests such as magnetic resonance angiography (MRA), computed tomographic angiography (CTA) and transcranial Doppler (TCD) have been advocated as alternatives to intra-arterial digital subtraction angiography to screen for aneurysms. Although all are promising techniques, the quality of data testing their accuracy is limited. Overall reported sensitivity for CTA and MRA (TCD is poorer) was 76-98% and specificity was 85-100%, but many subjects had an aneurysm or recent SAH, which could overestimate accuracy. CTA and MRA are much poorer methods for the detection of aneurysms <5 mm diameter, which account for up to one-third of unruptured aneurysms. Elective surgical clipping of asymptomatic aneurysms has a morbidity of 10.9% and mortality of 3. 8%. Treatment of aneurysms by Guglielmi coils, for which there is less long-term follow-up available, has a 4% morbidity and 1% mortality, but only achieves complete aneurysm occlusion in 52-78% of cases. There has been interest in screening for aneurysms, but the indication for, and cost effectiveness of screening are unclear because aneurysm prevalence varies, rupture rate is low, non-invasive imaging tests are not yet accurate enough to exclude small aneurysms and the morbidity and mortality for elective surgical treatment of unruptured aneurysms is high. There may be a limited role for investigation of high risk subgroups. Ideally, screening in such subgroups should be tested in a randomized trial. The avoidance of risk factors for aneurysms such as smoking, hypertension and hypercholesterolaemia should be part of the management of at-risk subjects.
488 citations
Cites background from "The familial occurrence of intracra..."
...3%, but was as high as 9% in studies which looked specifically for aneurysms (Bannerman et al., 1970)....
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...Prior to the 1970s, several autopsy studies suggested that the overall prevalence of unruptured aneurysms in adults was as low as 0.3%, but was as high as 9% in studies which looked specifically for aneurysms (Bannerman et al., 1970)....
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TL;DR: The congenital theory of the etiology of intracranial berry aneurysms has been widely accepted for many years but review of the supporting evidence indicates that it is not based on sound scientific data but on unscientific and unsubstantiated allegations.
Abstract: The congenital theory of the etiology of intracranial berry aneurysms has been widely accepted for many years. Review of the supporting evidence indicates that it is not based on sound scientific data but on unscientific and unsubstantiated allegations. There is no evidence of a congenital, developmental, or inherited weakness of the vessel wall. The most plausible explanation is that the aneurysms are acquired degenerative lesions--the effect of hemodynamic stress. The mural atrophy leading to aneurysmal dilatation is an acquired lesion which can be produced experimentally by hemodynamics alone. Hypertension and connective tissue disorders associated with acquired loss of tensile strength of the connective tissues are not essential: they appear to be aggravating rather than causal factors. Occlusion of one or more feeding vessels may enhance the possibility of aneurysm formation at large arterial forks subjected to the augmented hemodynamic stress associated with collateral flow.
420 citations
Journal Article•
344 citations
TL;DR: Recognition of an underlying generalized connective tissue disorder may be of considerable importance, although marked phenotypic heterogeneity often complicates the diagnosis of these disorders.
Abstract: Heritable disorders of connective tissue are recognized in a small minority of patients with neurovascular diseases. In this report, we review the neurovascular manifestations of four heritable connective tissue disorders: Ehlers-Danlos syndrome, Marfan's syndrome, osteogenesis imperfecta, and pseudoxanthoma elasticum, as well as two other systemic disorders with potential vascular manifestations: neurofibromatosis and polycystic kidney disease.Typical neurovascular complications of Ehlers-Danlos syndrome are carotid-cavernous fistulae, intracranial aneurysms, and cervical artery dissections. Arterial dissections and intracranial aneurysms cause the majority of neurovascular symptoms in Marfan's syndrome. Neurovascular disease is uncommon in osteogenesis imperfecta, although carotid-cavernous fistulae and vertebral artery dissections have been reported. Neurovascular disease in pseudoxanthoma elasticum is characterized by intracranial aneurysms and cerebral ischemia caused by premature arterial occlusive ...
336 citations
TL;DR: Most studies were performed in populations with high aneurysm prevalence, which may have introduced bias toward noninvasive examinations, and CT angiography and MRAngiography depicted aneurYSms with an accuracy of about 90%.
Abstract: PURPOSE: To perform a systematic review to determine the accuracy of computed tomographic (CT) angiography, magnetic resonance (MR) angiography, and transcranial Doppler ultrasonography (US) in depicting intracranial aneurysms. MATERIALS AND METHODS: A 1988–1998 literature search for studies with 10 or more subjects in which noninvasive imaging was compared with angiography was undertaken. Studies meeting initial criteria were evaluated by using intrinsically weighted standardized assessment to determine suitability for inclusion. Studies scoring greater than 50% were included. RESULTS: Of 103 studies that met initial criteria, 38 scored greater than 50%. CT angiography and MR angiography had accuracies per aneurysm of 89% (95% CI: 87%, 91%) and 90% (95% CI: 87%, 92%), respectively. For US, data were scanty and accuracy was lower, although the CIs overlapped those of CT angiography and MR angiography. Sensitivity was greater for detection of aneurysms larger than 3 mm than for detection of aneurysms 3 mm ...
324 citations
References
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Journal Article•
344 citations
Journal Article•
TL;DR: The remainder of the book is devoted to detailed clinical descriptions of the rare syndromes previously enumerated, together with a full account of what is known of their mode of inheritance.
Abstract: In the whole field of Medicine, it would be hard to pick a related series of problems more difficult than those considered in this book. The physiology of connective tissue is poorly understood; its chemistry is fragmentary; and it is not even certain that connective tissue can justifiably be treated as an entity. The inherited diseases of this enigmatic body component consist of a series of weird conditions, all rare, such as the Marfan and EhlersDanlos syndromes, osteogenesis imperfecta, pseudoxanthoma elasticum and the Hurler syndrome (gargoylism). Although these varied syndromes are readily recognisable in their fully-developed forms, patients frequently display only a few incomplete features. Since there are no specific biochemical tests at present available diagnosis has to be based on appraisal of the clinical phenomena alone, and hence is often uncertain. The medical geneticist has therefore to feel his way through a swamp of uncertainty, with only rare islets of fact on which to place his feet. The skill with which Dr. McKusick performs this difficult feat is really remarkable. Although primarily a clinician, he has marshalled what little is known of the biology and chemistry of connective tissue in a useful preliminary chapter; and in another, has provided a brilliant summary of what medical genetics is about, which should be read by any clinician who is thinking of entering this field. The remainder of the book is devoted to detailed clinical descriptions of the rare syndromes previously enumerated, together with a full account of what is known of their mode of inheritance. Anyone interested in this group of diseases will find this book quite indispensable.
316 citations
"The familial occurrence of intracra..." refers background in this paper
...These include: [ 11 continued detailed study of familial cases of intracranial aneurysms, [ 21 study of intracranial aneurysm in twins, [3] the incidence of symptoms of cerebral aneurysms in different ethnic groups in life, [4] the autopsy incidence in different ethnic groups, and [5] genetic characteristics such as blood groups and other markers in affected persons in both sporadic and familial cases....
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TL;DR: Age 20: Rupture of splenic artery; emergency splenectomy Age 25: Large femoral haematoma; required blood transfusion; E.D.S. diagnosed Age 30: Died of spontaneous rupture of the aorta
Abstract: Age 20: Rupture of splenic artery; emergency splenectomy Age 25: Large femoral haematoma; required blood transfusion; E.D.S. diagnosed Age 27: Recurrent severe abdominal pain; all investigations nega tive Age 12: Large haematoma in right iliac fossa Age 17: Large haematoma in left popliteal fossa Age 24: Large haematoma in right popliteal fossa; required blood transfusion; E.D.S. diagnosed Age 30: Died of spontaneous rupture of the aorta
169 citations
TL;DR: The histopathological features of the intracranial blood vessels suggests that the vascular defects in this case can be explained, in part, on the basis of the anatomical peculiarities of the generalized connective tissue disorder.
Abstract: THE EHLEHS-DANLOS SYNDROME is a n hereditary abnormality of the connective tissue of the body. The primary clinical feature of this disorder, cutis hyperelastica or hyperelasticity of the skin, was first described in 1682 by Job van Meekeren,l a Dutch physician. Little was added to this description until 1901 when Ehlei-s‘ described a n increased mobility of joints and a frequently associated bruising tendency. In 1908, Danlos3 recognized the subcutaneouy tumors (pseudotumors) which sometimes accompany the syndrome. A variety of associated clinical manifestations, including muscular hypotonicity, congenital heart defects, diaphragmatic hernia, ectasia of viscera, spontaneous rupture of the lung, and gastrointestinal diverticula, have been described. In addition to the classical manifestations of the condition, the following case of EhlersDanlos syndrome demonstrates an hitherto unreported association-multiple intracranial aneurysms. The histopathological features of the intracranial blood vessels suggests that the vascular defects in this case can be explained, in part, on the basis of the anatomical peculiarities of the generalized connective tissue disorder.
114 citations
"The familial occurrence of intracra..." refers background in this paper
...It is concluded that familial aggregation may be related to [ 11 known hereditary disorders, such as the Ehlers-Danlos syndrome, in which intracranial aneurysm may be a complication, [ 2 ] familial aneurysms in which genetic factors may have an important role, especially where there is anatomical concordance in lesions, and [3] fortuitous familial aggregation....
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...These include: [ 11 continued detailed study of familial cases of intracranial aneurysms, [ 21 study of intracranial aneurysm in twins, [3] the incidence of symptoms of cerebral aneurysms in different ethnic groups in life, [4] the autopsy incidence in different ethnic groups, and [5] genetic characteristics such as blood groups and other markers in affected persons in both sporadic and familial cases....
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TL;DR: This disorder is characterized by hyperelasticity of the skin, hyperextensibility of the joints, and histories of "easy bruising" with cutaneous hemorrhage and prolonged poorly controlled bleeding with surgical procedures.
Abstract: THE PROTEAN manifestations of Ehlers-Danlos syndrome, a rare disease of congenital nature involving body structures of mesodermal origin, are well known. Considered as a disturbance of the connective tissue, the abnormality concerns mainly the elastic and more particularly the collagen tissue throughout the body. This disorder is characterized by hyperelasticity of the skin, hyperextensibility of the joints, and histories of "easy bruising" with cutaneous hemorrhage and prolonged poorly controlled bleeding with surgical procedures. More dramatic manifestations of the disorder in other organ systems occur, eg, spontaneous rupture of the heart and lung, ectasia of the viscera, cardiac anomalies, diaphragmatic hernia, and gastrointestinal diverticula. Recently, Rubenstein and Cohen 13 described as unique a patient with Ehlers-Danlos syndrome associated with multiple intracranial aneurysms and spontaneous subarachnoid hemorrhage. Aneurysm of the larger vessels (aorta) has been recorded by McKusick 12 in this syndrome. There appears to be only one reference in the
89 citations