Neurovascular Anomalies Research Articles

Endovascular management of pediatric pial arteriovenous fistulas with hereditary GDF2 mutation: illustrative case.

Intracranial pial arteriovenous fistulas (PAVFs) are uncommon neurovascular anomalies that primarily affect the pediatric population. PAVFs are often linked to hereditary hemorrhagic telangiectasia, yet the specific genetic mutations remain unidentified. While endovascular embolization is the preferred treatment for PAVFs, complications like hydrocephalus and sinus thrombosis pose challenges in management. The authors present a rare case of PAVF in a 6-month-old male neonate with a hereditary GDF2 mutation, where the fistula was supplied by the posterior inferior cerebellar artery and drained directly into the sigmoid sinus. The PAVF was effectively treated with endovascular embolization using coils and Onyx. Furthermore, the authors describe the successful use of rivaroxaban in managing subsequent sinus thrombosis after the embolization of PAVFs. Additionally, the authors review treatment strategies and complications following fistula disconnection. Endovascular embolization is the primary treatment choice for the majority of pediatric PAVFs, while a hereditary GDF2 mutation is considered a potential contributing factor to the formation of these malformations in children. Rivaroxaban has shown promise as an effective therapeutic option for pediatric sinus thrombosis, supported by its established safety profile. https://thejns.org/doi/10.3171/CASE24182.

Imaging Assessment of Fetal Cerebrovascular Anomalies.

Four distinct vascular anomalies can be seen to affect the brain on fetal imaging: vein of Galen malformations, non-galenic arteriovenous pial fistulas, dural sinus malformations, and intracranial venous malformations. These congenital disorders affect the arteries and veins of the developing brain and are rarely seen beyond the neonatal stage. The four fetal cerebrovascular anomalies are associated with quite disparate natural histories and prognoses. MRI plays a pivotal role in the evaluation of fetuses with these conditions due to its ability to definitively establish the diagnosis, to detect subtle parenchymal injuries, to delineate the course of abnormal vessels in detail and to some extent the nature of vascular flow, and to identify ischemic, thrombotic, and hemorrhagic complications. Recently, an investigational transurterine embolization procedure targeted at treating fetuses with vein of Galen malformations who are at high risk for neonatal decompensation has emerged as a promising alternative to expectant management and post-natal embolization, with imaging being used to identify suitable patients for the intervention and in pre-procedural planning. This manuscript reviews the essential imaging and clinical features of these four fetal neurovascular anomalies and underscores the practical aspects related to counseling, prognosis, and the multidisciplinary management of these entities.ABBREVIATIONS: ACVRL1= activin A receptor like type 1; b-SSFP=Balanced Steady State Free precession; DSM= Dural Sinus Malformation; Ephrin B4= Ephrin type-B receptor 4; icVM= Intracranial Venous Malformation; ITGB1= Integrin Subunit Beta 1; NOTCH1= Neurogenic locus notch homolog protein 1; PTPN11= Protein Tyrosine Phosphatase Non-Receptor Type 11; RASA1= RAS P21 Protein Activator 1; SSFSE= Single-shot fast spin echo; VOGM=Vein of Galen Malformation.

Germline genetic mutations in pediatric cerebrovascular anomalies: a multidisciplinary approach to screening, testing, and management.

Genetic alterations are increasingly recognized as etiologic factors linked to the pathogenesis and development of cerebrovascular anomalies. Their identification allows for advanced screening and targeted therapeutic approaches. The authors aimed to describe the role of a collaborative approach to care and genetic testing in pediatric patients with neurovascular anomalies, with the objectives of identifying what genetic testing recommendations were made, the yield of genetic testing, and the implications for familial screening and management at present and in the future. The authors performed a descriptive retrospective cohort study examining pediatric patients genetically screened through the Pediatric Neurovascular Program of a single treatment center. Patients 18 years of age and younger with neurovascular anomalies, diagnosed radiographically or histopathologically, were evaluated for germline genetic testing. Patient demographic data and germline genetic testing and recommendation, clinical, treatment, and outcome data were collected and analyzed. Sixty patients were included; 29 (47.5%) were female. The mean age at consultation was 11.0 ± 4.9 years. Diagnoses included cerebral arteriovenous malformations (AVMs) (n = 23), cerebral cavernous malformations (n = 19), non-neurofibromatosis/non-sickle cell moyamoya (n = 8), diffuse cerebral proliferative angiopathy, and megalencephaly-capillary malformation. Of the 56 patients recommended to have genetic testing, 40 completed it. Genetic alterations were found in 13 (23%) patients. Four patients with AVMs had RASA1, GDF2, and ACVRL1 mutations. Four patients with cavernous malformations had Krit1 mutations. One with moyamoya disease had an RNF213 mutation. Three patients with megalencephaly-capillary malformation had PIK3CA mutations, and 1 patient with a cavernous sinus lesion had an MED12 mutation. The majority of AVM patients were treated surgically. Patients with diffuse cerebral proliferative angiopathy were treated medically with sirolimus. At-risk relatives of 3 patients positive for genetic anomalies had also been tested. This study demonstrates a role for exploring genetic alterations in the identification and treatment of pediatric neurovascular disease pathogenesis. Germline genetic mutations were found in almost one-quarter of the patients screened in this study, results that helped to identify medically targeted treatment modalities for some pediatric neurovascular patients. Insight into the genetic etiology of vascular anomalies may provide broader clinical implications for risk assessment, family screening, follow-up surveillance, and medical management.

Distribution of Cerebrovascular Phenotypes According to Variants of the ENG and ACVRL1 Genes in Subjects with Hereditary Hemorrhagic Telangiectasia.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder caused, in more than 80% of cases, by mutations of either the endoglin (ENG) or the activin A receptor-like type 1 (ACVRL1) gene. Several hundred variants have been identified in these HHT-causing genes, including deletions, missense and nonsense mutations, splice defects, duplications, and insertions. In this study, we have analyzed retrospectively collected images of magnetic resonance angiographies (MRA) of the brain of HHT patients, followed at the HHT Center of our University Hospital, and looked for the distribution of cerebrovascular phenotypes according to specific gene variants. We found that cerebrovascular malformations were heterogeneous among HHT patients, with phenotypes that ranged from classical arteriovenous malformations (AVM) to intracranial aneurysms (IA), developmental venous anomalies (DVA), and cavernous angiomas (CA). There was also wide heterogeneity among the variants of the ENG and ACVRL1 genes, which included known pathogenic variants, variants of unknown significance, variants pending classification, and variants which had not been previously reported. The percentage of patients with cerebrovascular malformations was significantly higher among subjects with ENG variants than ACVRL1 variants (25.0% vs. 13.1%, p < 0.05). The prevalence of neurovascular anomalies was different among subjects with different gene variants, with an incidence that ranged from 3.3% among subjects with the c.1231C > T, c.200G > A, or c.1120C > T missense mutations of the ACVRL1 gene, to 75.0% among subjects with the c.1435C > T missense mutation of the ACVRL1 gene. Further studies and larger sample sizes are required to confirm these findings.

Spinal Neurovascular Malformations in Klippel-Trenaunay Syndrome: A Single Center Study.

A number of studies have demonstrated spinal anomalies associated with Klippel-Trenaunay syndrome (KTS). To date, there are no large consecutive series examining the prevalence and subtype distribution of spinal neurovascular malformations in patients with KTS. To report the spectrum and incidence of spinal neurovascular manifestations in the KTS population. This was a cross-sectional study. Consecutive patients with definite KTS as defined by International Society for the Study of Vascular Anomalies criteria who underwent spinal neuroimaging at our institution were included. All studies were evaluated by a staff neuroradiologist and a senior radiology resident for the presence of developmental venous anomalies, cavernous malformations (CMs), and arteriovenous shunts (AVS). A total of 116 patients with definite KTS who underwent spinal neuroimaging were included. A total of 23 neurovascular anomalies were found in 19 patients (16.4%), including 4 patients with multiple anomalies. These included 5 patients with spinal cord CMs (4.3%), 14 patients with a paraspinal or epidural venous malformation (12.1%), and 4 patients with an AVS (3.4%). Of the AVS, 3 were epidural arteriovenous fistulas, 1 of which likely formed de novo in an epidural venous malformation. One was a conus medullaris arteriovenous malformation. Our study cohort of 116 KTS patients demonstrated a wide spectrum of spinal neurovascular anomalies with a relatively high prevalence. Potential phenotypic descriptions of KTS should include the possibility for spinal neurovascular anomalies.

Detection of clustered anomalies in single-voxel morphometry as a rapid automated method for identifying intracranial aneurysms.

Unruptured intracranial aneurysms (UIAs) are prevalent neurovascular anomalies which, in rare circumstances, rupture to cause a catastrophic subarachnoid haemorrhage. Although surgical management can reduce rupture risk, the majority of UIAs exist undiscovered until rupture. Current clinical practice in the detection of UIAs relies heavily on manual radiological review of standard imaging modalities. Recent computer-aided UIA diagnoses can sensitively detect and measure UIAs within cranial angiograms but remain limited to low specificities whose output also requires considerable radiologist interpretation not amenable to broad screening efforts. To address these limitations, we have developed a novel automatic pipeline algorithm which inputs medical images and outputs detected UIAs by characterising single-voxel morphometry of segmented neurovasculature. Once neurovascular anatomy of a specified resolution is segmented, correlations between voxel-specific morphometries are estimated and spatially-clustered outliers are identified as UIA candidates. Our automated solution detects UIAs within magnetic resonance angiograms (MRA) at unmatched 86% specificity and 81% sensitivity using 3 min on a conventional laptop. Our approach does not rely on interpatient comparisons or training datasets which could be difficult to amass and process for rare incidentally discovered UIAs within large MRA files, and in doing so, is versatile to user-defined segmentation quality, to detection sensitivity, and across a range of imaging resolutions and modalities. We propose this method as a unique tool to aid UIA screening, characterisation of abnormal vasculature in at-risk patients, morphometry-based rupture risk prediction, and identification of other vascular abnormalities.

Intracranial and extracranial vascular manifestations of patients with a clinical diagnosis of Klippel-Trenaunay syndrome.

While numerous reports have demonstrated intracranial CNS anomalies associated with Klippel-Trenaunay syndrome, to our knowledge, there has not been a large consecutive study examining these anomalies. The aim of this study was to determine the spectrum of intracranial neurovascular manifestations in patients with a clinical diagnosis of Klippel-Tranaunay syndrome. Consecutive patients with a clinical diagnosis of Klippel-Trenaunay syndrome, as defined by the International Society for the Study of Vascular Anomalies, who underwent brain contrast-enhanced CT/computed tomography angiography, MRI/magnetic resonance angiography, or digital subtraction angiography at our institution from 2000 to 2019 were included. Studies were evaluated by a neuroradiologist and a senior radiology resident for the presence of cavernous malformations, developmental venous anomalies, venous sinus developmental abnormalities, craniofacial venous malformations, intraosseous venous malformations, and intracranial/extracranial venous abnormalities. Fifty patients with definite KTS were included. Thirty-four neurovascular anomalies were found in 17 patients (34.0%), including 8 with multiple anomalies. Nine patients had developmental venous anomalies (18.0%), 7 had craniofacial venous malformations (14.0), 6 had venous sinus developmental abnormalities (12.0%), 7 had intraosseous venous malformations (14.0%), and 2 had cavernous malformations (4.0%), and 9 patients had both intracranial venous abnormalities and craniofacial or calvarial findings (13.0%). Our findings demonstrate that Klippel-Trenaunay syndrome can involve a wide spectrum of intracranial neurovascular anomalies predominantly involving the venous system.

Carpal Tunnel Syndrome Secondary to Acute Thrombosis of Persistent Median Artery and Review of the Literature

Carpal tunnel syndrome (CTS) is the most common neuropathy of the upper extremity.1 We report a case in which a twenty-eight-year-old manual labourer presented with acute thrombosis in a persistent median artery which triggered acute carpal tunnel symptoms. A bifid median nerve was found upon carpal tunnel release. The knowledge of the existence of this anatomic variation is important in order to prevent inadvertent injury. We further discuss the possible aetiologies for CTS as well as neurovascular anomalies which may lead to median nerve compression at the wrist.

Anomalies of radial and ulnar arteries

During dissection conducted in an anatomy department of the right upper limb of the cadaver of a 70-year-old male, both origin and course of the radial and ulnar arteries were found to be anomalous. After descending 5.5 cm from the lower border of the teres major, the brachial artery anomalously bifurcated into a radial artery medially and an ulnar artery laterally. In the arm, the ulnar artery lay lateral to the median nerve. It followed a normal course in the forearm. The radial artery was medial to the median nerve in the arm and then, at the level of the medial epicondyle, it crossed from the medial to the lateral side of the forearm, superficial to the flexor muscles. The course of the radial artery was superficial and tortuous throughout the arm and forearm. The variations of radial and ulnar arteries described above were associated with anomalous formation and course of the median nerve in the arm. Knowledge of neurovascular anomalies are important for vascular surgeons and radiologists.

The scalp hair collar and tuft signs: A retrospective multicenter study of 78 patients with a systematic review of the literature

Hair collar sign (HCS) and hair tuft of the scalp (HTS) are cutaneous signs of an underlying neuroectodermal defect, but most available data are based on case reports. We sought to define the clinical spectrum of HCS and HTS, clarify the risk for underlying neurovascular anomalies, and provide imaging recommendations. A 10-year multicenter retrospective and prospective analysis of clinical, radiologic, and histopathologic features of HCS and HTS in pediatric patients was performed. Of the 78 patients included in the study, 56 underwent cranial and brain imaging. Twenty-three of the 56 patients (41%) had abnormal findings, including the following: (1) cranial/bone defect (30.4%), with direct communication with the central nervous system in 28.6%; (2) venous malformations (25%); or (3) central nervous system abnormalities (12.5%). Meningeal heterotopia in 34.6% (9/26) was the most common neuroectodermal association. Sinus pericranii, paraganglioma, and combined nevus were also identified. The partial retrospective design and predominant recruitment from the dermatology department are limitations of this study. Infants with HCS or HTS are at high risk for underlying neurovascular anomalies. Magnetic resonance imaging scans should be performed in order to refer the infant to the appropriate specialist for management.

Management and Leadership: Educating and Orienting the Radiology Nurse of the Future

VOLUME 30 ISSUE 3 The specialty of radiology has undergone dramatic growth and change over the past 30 years, largely because of the tremendous advances in imaging capabilities. These advances have changed the way we approach such problems as appendicitis, neurovascular anomalies, abscesses, uterine fibroids, and abdominal aortic aneurysmsdconditions that were once life threatening are now treated with ease. Radiology has moved from being purely a diagnostic specialty (taking films and identifying diseases and/or problems) to invasive, procedural, and curative medicine. As a response, the role of the radiology nurse has evolved. Today, the radiology nurse is an integral element of patient care for individuals undergoing radiological procedures. In the past, a patient presenting with an acute abdomen would often require an exploratory laparotomy merely to identify and treat the underlying problem. Today an image often gives a diagnosis, slowing the rush to surgery and even negating the need for surgery at all. The shift has been away from traditional open surgical approaches performed within the operating room using anesthesia, to procedures performed in the interventional radiology department using percutaneous approaches. Developments in imaging and interventional radiology now offer different ways of diagnosing, treating

PHACE syndrome: MRI of intracerebral vascular anomalies and clinical findings in a series of 12 patients

PHACE (posterior fossa defects, haemangioma, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities) syndrome describes a constellation of abnormalities that can occur in association with segmental craniofacial infantile haemangioma. To report the spectrum of clinical and imaging abnormalities seen in a cohort of children. A retrospective review of the clinical and imaging records of all patients diagnosed with PHACE syndrome between 1998 and 2009 was performed. Information sought included patient demographics, craniofacial segments involved, imaging findings and other extracutaneous abnormalities. Twelve patients were diagnosed with PHACE syndrome over 11 years. All patients had a segmental craniofacial haemangioma. Involved facial segments, in order of frequency, were frontotemporal (12), maxillary (8), mandibular (5) and frontonasal (1). The most common extracutaneous abnormalities were neurovascular anomalies (10), with many patients having multiple anomalies. The spectrum of arterial anomalies ranged from hypoplasia (9) to ectasia (3), anomalous origin/course (2) and persistent fetal anastomosis (2). Other anomalies found included cardiac anomalies (3), coarctation of the aorta (2), posterior fossa malformations (1) and sternal region anomalies (1). Intracranial anomalies are the most common extracutaneous feature of PHACE syndrome. The contribution of the radiologist in the recognition of such anomalies is important for the diagnosis of PHACE syndrome.

Parry–Romberg syndrome associated with unusual intracranial vascular malformations and Phthisis bulbi

Neurovascular anomalies of Parry–Romberg syndrome have been reported infrequently. We report a case of Parry–Romberg syndrome with hypoplastic left internal carotid, middle cerebral, anterior cerebral, posterior communicating and posterior cerebral artery. The patient presented with partial seizures, hemiparesis and phthisis bulbi.

Asymptomatic neurovascular anomalies in PHACES syndrome: Findings on screening MRI And MRA in 5 children

Asymptomatic neurovascular anomalies in PHACES syndrome: Findings on screening MRI And MRA in 5 children

Mendelian hypertension with brachydactyly as a molecular genetic lesson in regulatory physiology.

Mendelian forms of hypertension have delivered a treasure trove of novel genes. To date, the molecular mechanisms of five such syndromes have been largely clarified, including glucocorticoid-remediable aldosteronism, Liddle's syndrome, apparent mineralocorticoid excess, an activating mutation of the mineralocorticoid receptor, and pseudohypoaldosteronism type 2. Each of these conditions features salt sensitivity with increased sodium and volume reabsorption by the kidney and low plasma renin activity. None of the gene loci for these syndromes has been convincingly linked to hypertension in the general population. We are investigating kindreds who have autosomal-dominant hypertension and brachydactyly. Affected persons invariably have both anomalies. The hypertension is severe and results in death at about age 50 years from stroke. The condition resembles essential hypertension, because renin, aldosterone, and norepinephrine responses are normal and no salt sensitivity is present. The response to antihypertensive drugs is general. Another feature is diminished baroreflex sensitivity with markedly impaired blood pressure buffering. Furthermore, the ventrolateral medulla may be compromised in these patients, because neurovascular anomalies are a regular finding. We mapped the gene(s) for this disease to chromosome 12p and narrowed the chromosomal region by studying more affected families. Interestingly, the same locus was recently mapped in Chinese families with essential hypertension. Our 3-centimorgan region contains genes encoding a phosphodiesterase, an ATP-dependent potassium channel, and its regulator the sulfonylurea receptor 2. Screening of the coding regions revealed that none of these candidate genes harbor obvious mutations; however, other genetic mechanisms may nevertheless compromise their function. Our study underscores the importance of regulatory physiology to the understanding of a complex genetic syndrome.

Syndactyly

Syndactyly is a common congenital anomaly that interferes with normal hand function. Inheritable, spontaneous, and syndromic forms have been identified with various similarities and dissimilarities. Inheritable syndactylism is associated with genetic defects involving particular candidate regions on the second chromosome. Syndactyly separation follows established principles with regard to timing, technique, and postoperative management. Early release of border digits is mandatory to promote function and prevent contracture. Proper flap design provides commissure reconstruction and avoids the use of skin graft within the web space. Identification of neurovascular anomalies and preservation of critical vascular inflow preserves digital perfusion. Postoperative dressings provide compression to skin-grafted areas and protection to the underlying digits. Adherence to recognized principles yields acceptable results, although complications can emerge requiring additional management. Copyright © 2001 by the American Society for Surgery of the Hand

Double gluteus maximus muscle with associated variations in the gluteal region.

We report bilateral muscular and neurovascular anomalies of the gluteal region in a cadaver. On the right side, the gluteus maximus muscle had two parts, one of which was fibrous and the other muscular. In addition, there were duplicated piriformis muscles and high division of the sciatic nerve. The common peroneal nerve passed between the two parts of the piriformis muscle, and the tibial nerve emerged from under the lower piriformis muscle (infrapiriform foramen). At the same time the internal pudendal vessels and pudendal nerve passed over the sacrotuberous ligament on the left side. The double piriformis muscles and high division of the nerve are known as an anomaly which is believed to cause a nerve compression syndrome called the syndrome of the piriformis muscle. To the best of our knowledge anomalies of the gluteus maximus muscle and pudendal structures have not yet been reported. This complex anomaly should be kept in mind in connection with intramuscular injections of the gluteal region, the piriformis syndrome, and the surgery of this region.

Neurovascular compression at the ventrolateral medulla in autosomal dominant hypertension and brachydactyly.

Autosomal dominant hypertension with brachydactyly features severe hypertension that causes stroke usually before the age of 50 years. We recently characterized the hypertension as featuring normal renin, aldosterone, and catecholamine responses and mapped the gene responsible to chromosome 12p. Since angiography in an affected subject had earlier shown tortuous vessels, we performed magnetic resonance tomography (MRT) angiography to look for possible neurovascular anomalies (NVA), which have been previously associated with hypertension. NVA can be caused by a looping posterior inferior cerebellar or vertebral artery. Experimental and clinical evidence suggests that NVA may cause hypertension by a compression of the ventrolateral medulla. We performed MRT in 15 hypertensive affected (aged 14 to 57 years) and 12 normotensive nonaffected (aged 12 to 59 years) family members. We then tested for linkage between the hypertension-brachydactyly phenotypes and the presence of NVA. All 15 affected persons had MRT evidence for NVA. All had left-sided posterior inferior cerebellar artery or vertebral artery loops, while 6 had bilateral NVA. None of the nonaffected family members had NVA. The phenotypes were linked with an LOD score of 9.2 given a penetrance of 99%. Autosomal dominant hypertension and brachydactyly regularly feature NVA, which is frequently bilateral. The early age at which NVA was identified suggests that the condition is primary. We suggest that NVA may be involved in the pathogenesis of this form of hypertension and perhaps essential hypertension as well. Further studies are necessary to address the question of causation.

The neurovascular complications of cocaine

Cocaine use has been temporally associated with neurovascular complications, including the rupture of intracerebral aneurysms. The purpose of the current study was to determine the type of neurovascular complications associated with cocaine use in our patient population, the temporal relationship between cocaine use and their onset, and whether cocaine users with subarachnoid hemorrhage (SAH) presented with smaller aneurysms at an earlier age than a control group of noncocaine users with SAH. Thirty-three patients who presented to the Detroit Medical Center with neurovascular sequelae associated with cocaine use were identified. All patients were chronic cocaine users who related a history of recent use confirmed by a drug screen. Cocaine users with SAH were compared to a control group of 44 patients with SAH who presented without evidence of cocaine use. Sixteen patients presented with SAH. Twelve patients subsequently underwent four-vessel cerebral arteriogram revealing 14 aneurysms; six patients presented with intracerebral hemorrhage (ICH) and seven patients with evidence of ischemic stroke. Eighteen (54.5%) patients noted onset of their symptoms while using cocaine, 87.9% noted onset within 6 hours of use. Delayed presentation occurred predominantly in patients who suffered ischemic strokes. The average age of patients who used cocaine and presented with SAH secondary to a ruptured intracerebral aneurysm was 32.8 years with an average aneurysm diameter of 4.9 mm versus an average age of 52.2 years with an average aneurysm diameter of approximately 11.0 mm in noncocaine users. Population differences were statistically significant at the p < 0.05 level. Mortality was 27.3% for patients who presented with neurovascular sequelae of their cocaine use, with 77.8% of deaths occurring in patients who presented with SAH. Chronic cocaine use appears to predispose patients who harbor incidental neurovascular anomalies to present at an earlier point in their natural history than similar non-cocaine users.

Neurovascular manifestations of heritable connective tissue disorders. A review.

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 disease. Intracranial occlusive arterial disease is the most common neurovascular manifestation of neurofibromatosis, followed by cervical arteriovenous fistulae and aneurysms and intracranial aneurysms. Intracranial aneurysms are the hallmark of polycystic kidney disease. Recognition of an underlying generalized connective tissue disorder may be of considerable importance, although marked phenotypic heterogeneity often complicates the diagnosis of these disorders. Conversely, the association of certain neurovascular anomalies with generalized connective tissue disorders and recognition of their basic molecular defect may offer clues to the etiology and pathogenesis of these neurovascular diseases in general.