Arterial Fibromuscular Dysplasia

Subject Review Arterial Fibromuscular Dysplasia

THOMAS F. LUSCHER, M.D.,* Department of Physiology and Biophysics; J. T. LIE, M.D., Department of Pathology; ANTHONY W. STANSON, M.D., O. WAYNE HOUSER, M.D., Department of Diagnostic Radiology; LARRY H. HOLLIER, M.D.,f Section of Vascular Surgery; SHELDON G. SHEPS, M.D., Division of Hypertension and Internal Medicine Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease that involves primarily the renal and internal carotid arteries and less often the vertebral, iliac, subclavian, and visceral arteries. Although its pathogenesis is not completely understood, humoral, mechanical, and genetic factors as well as mural ischemia may play a role. The natural history is relatively benign, with progression occurring in only a minority of the patients. Typical clinical manifestations are renovascular hypertension, stroke, subarachnoid hemorrhage, abdominal angina, or claudication of the legs or arms. In patients with symptoms, percutaneous transluminal angioplasty has emerged as the treatment of choice in most involved vascular beds.

Fibromuscular dysplasia (FMD), or fibromus- His blood pressure was normal after nephreccular hyperplasia, is a nonatherosclerotic and tomy. Histologically, the main renal artery apnoninflammatory vascular disease that pri- peared to be partially obstructed by "an intramarily involves the medium-sized and small luminal mass of smooth muscle"; more distally, arteries, most commonly the renal and carotid the arterial wall was thinned. The lesion shown arteries 1 (Fig. 1). Young Caucasian women are in Figure 6 of their article, however, is likely a predominantly affected. The patients may be histologic artifact rather than the first genuine asymptomatic or may have the initial mani- case of FMD. In 1958, McCormack and assofestations of hypertension, stroke, abdominal ciates 3 introduced the term "fibromuscular hyperangina, or other symptoms of vascular insuffi- plasia" when describing three young patients ciency, depending on the vascular bed involved with renovascular hypertension and an unusual type of renal artery stenosis. and the severity of the stenosis. Initially, the lesion was thought to be confined The first description of FMD, long before the term was introduced into the medical literature, to the renal artery. Later, however, it became has often been attributed to Leadbetter and Burk- obvious that other arteries, such as the carotid land. 2 In 1938, they reported on a 5V2-year-old boy and vertebral, 4-6 the subclavian and axillary, 6,7 with hypertension and an ectopic right kidney. the mesenteric, hepatic, and splenic, 6,8,9 and the iliac, 6 could be involved as well. An association between FMD and coarctation of the abdominal aorta has also been described in a few cases. 6,10 11 *Present address: Division of Cardiology, University Hospi- Coronary FMD seems to be extremely rare. tal, Basel, Switzerland. Although FMD is thought to be strictly an fPresent address: Ochsner Clinic, New Orleans, Louisiana. arterial disease, involvement of the renal veins in one patient with FMD of the Address reprint requests to Dr. S. G. Sheps, Division of was confirmed Hypertension, Mayo Clinic, Rochester, MN 55905. renal artery. 12 Mayo Clin Proc 62:931-952, 1987

931

932

FIBROMUSCULAR DYSPLASIA

PREVALENCE A N D ANATOMIC DISTRIBUTION Information about the prevalence of FMD in patients with vascular disease is incomplete. In the hypertensive population, high blood pressure may be attributable to renovascular FMD in fewer than 2% of the patients. 13 In patients with renovascular hypertension, FMD is the under­ lying cause in 20 to 50%.14~16 FMD of the renal artery has also been found in healthy renal trans­ plant donors. 13 In an autopsy study of 819 con­ secutive examinations, 9 instances of renovas­ cular FMD were found, an incidence of about 1%.17 In patients undergoing carotid angiography, FMD was present in' 0.25 to 1%Λ13,1β,1β More than 1,400 patients with FMD in various vascular beds have been described in the liter­ ature. 5 Most (60 to 75%) of these patients had renovascular disease at the time of initial exami­ nation. Cerebrovascular FMD constitutes 25 to 30% of the published cases. 5,18,19 Similarly, in a study done at one institution, renovascular FMD was found in 75% and cerebrovascular FMD in 24% of 92 patients. 1 In this series, multivessel involvement seemed common (24%). In 9% of the patients, the mesenteric or subclavian arteries were involved as well, and 5% had FMD of the iliac arteries (Fig. 1). Systemic FMD involving the renal, mesenteric, iliac, and carotid arteries has been reported by others.6,13,20'21 PATHOLOGIC CLASSIFICATION A N D RADIOLOGIC APPEARANCE A pathologic classification of FMD was proposed by Harrison and McCormack 22 in 1971 and was revised by Stanley and colleagues 23 in 1975. The histologic classification is based on the pre­ dominant site of dysplasia in the arterial wall: the intima, media, or adventitia (Fig. 2). Hence, three main types of FMD have been identified— intimal fibroplasia, medial FMD, and periarterial or periadventitial fibroplasia. Lesions involving the medial layer of the artery may be further subdivided into medial fibroplasia, perimedial fibroplasia, and medial hyperplasia. 22 Originally, medial dissection had been considered a fourth subtype of medial FMD. Medial dissections, aneurysms, and arteriovenous fistulas, however, are complications of FMD and should not be classi­ fied as separate or distinct pathologic entities. Although this classification has been introduced for renovascular FMD, most types of the disorder

Mayo Clin Proc, October 1987, Vol 62

Typical FMD Atypical FMD

Fig. 1. Diagram of anatomic distribution of fibromuscular dysplasia (FMD) in arterial tree. About three-fourths of pa­ tients with FMD have renovascular disease and about onefourth have cerebrovascular disease. Other locations are less frequently affected. In some vascular beds, classic string-ofbeads stenoses are more common (typical FMD), whereas in others, other types of the disease seem to predominate (atypical FMD).

have also been noted in other vascular beds 23 (Fig. 3). This classification has the advantage of showing an excellent correlation between the angiographic appearance and the pathologic findings. 24,25 Medial FMD.—Among the three main fibro­ muscular vascular lesions, medial FMD is the most frequent type. The most common subtype,

Mayo Clin Proc, October 1987, Vol 62

FIBROMUSCULAR DYSPLASIA

933

Fig. 2. Diagram depicting histopathologic classification of arterial fibromuscular dysplasia, based on predominant site of involvement of arterial wall—intima (top), media (middle), and adventitia (bottom). (Modified from Harrison EG Jr, McCormack LJ.")

accounting for 70 to 95% of all fibromuscular vascular lesions, is medial fibroplasia. The angiographic appearance of this lesion is the classic string-of-beads stenoses (Fig. 3). Typically, the "beads" exceed the diameter of the proximal unaffected part of the artery. Multifocal thickened fibromuscular ridges alternating with areas of pronounced thinning of the vascular wall give rise to this phenomenon (Fig. 4). In the renal artery, the distal two-thirds is typically involved (Fig. 3 A). Often, the lesion extends into the branch arteries. In the cerebrovascular circulation, this type of FMD characteristically affects the internal carotid artery at the level of the C-l and C-2 vertebrae, sparing the origins and proximal segments of the major extracranial arteries 5,18 ' 25 (Fig. 3 B). This classic type of FMD also has been noted in the iliac 1,6 (Fig. 3 C), axillary, 7 and, in one patient, the epicardial coronary 26 arteries. In the subtype perimedial fibroplasia, some angiographic characteristics of string-of-beads stenoses may be evident. The "beads," however, are usually less numerous than in medial fibroFig. 3. Angiograms of medial fibroplasia in renal (A), internal plasia and are smaller in diameter than the carotid (B), and external iliac (C) arteries. Note typical string24 proximal unaffected part of the artery (Fig. 5). of-beads stenoses.

934

FIBROMUSCULAR DYSPLASIA

Mayo Clin Proc, October 1987, Vol 62

hyperplasia (Fig. 7 A and C). Histologically, it is characterized by a circumferential or eccentric accumulation of fibrous tissue in the intima (Fig. 6). The internal elastic lamina is always identifiable. 23 In contrast to other vascular diseases involving the intima, no inflammatory or lipid component is present, unless superimposed arteriosclerotic changes develop. 22 Both sexes seem to be affected with equal frequency. The lesion accounts for 1 to 5% of all fibromuscular arterial lesions. 22,23 In young patients, long tubular stenoses are more common, whereas smooth focal stenoses predominate in older patients. 23 True idiopathic intimal hyperplasia is rare and morphologically indistinguishable from atherosclerotic intimal fibrosis.

Fig. 4. Gross morphologic (A) and histopathologic (B) appearance of longitudinally sectioned internal carotid artery with typical medial fibromuscular dysplasia. Constriction of vascular lumen is caused by protruding dysplastic arterial media, and dilatation has resulted from segmentally deficient or absent media. (B, Elastic stain; x!6.)

Histologically, this type of FMD is characterized by extensive fibroplasia of the outer half of the media, and the external elastic membrane often is effaced22 (Fig. 6). It is found almost exclusively in women younger than 30 years of age who have right-sided renal artery stenosis, substantial collateral circulation, and hypertension. Clinically significant types of this lesion have been detected almost exclusively in the renal circulation. In the subtype medial hyperplasia, excessive medial smooth muscle without associated fibrosis causes focal concentric stenoses. The stenosis is usually subtotal, sometimes tubular, and smooth. In the renal artery, it typically involves the middle or distal part and does not affect branchings and segmental vessels. In the internal carotid artery, the lesion is characteristically found at the Cl-2 interspace. This unusual type of FMD probably accounts for fewer than 5% of fibroplastic stenoses. 22,23 Intimal Fibroplasia.—Intimal fibroplasia is angiographically indistinguishable from medial

Fig. 5. Angiogram of perimedial fibroplasia of right renal artery. Note atypical string-of-beads stenoses; "beads" are less numerous and smaller than in medial fibroplasia.

Mayo Clin Proc, October 1987, Vol 62

FIBROMUSCULAR DYSPLASIA

935

Periarterial (Periadventitial) Fibroplasia.—The rarest type of FMD is periarterial fibroplasia. In this disease, fibroplasia with collagen encompasses the adventitia and extends into the surrounding tissue (Fig. 6). Slight focal infiltration with lymphocytes and plasma cells may be present. 22

FMD is a histologic diagnosis; however, the diagnosis can be made with a high degree of accuracy on the basis of the angiographic appearance. Classic string-of-beads stenoses are consistent with FMD (Fig. 3). Both intimal and medial hyperplasia, however, may sometimes be confused with atherosclerotic plaques on an angiogram. Atherosclerotic stenoses are usually located within 1 cm of the orifice of the main renal or internal carotid artery and are typically eccentric. Furthermore, atherosclerotic renal artery stenoses are often associated with atherosclerotic changes in the abdominal aorta. FMD almost always involves the middle or distal segment of the renal or carotid artery, and the focal stenoses are concentric and typically have a smooth appearance. In their active stage, inflammatory vascular diseases usually are accompanied by laboratory evidence of inflammation. 28 Takayasu's arteritis has a different pattern of arterial involvement than FMD. In this arteritis, the aorta is almost always involved, and the large arteries are stenotic or, rarely, aneurysmal at and near their origin. Other types of vasculitis involve different and smaller arteries than those affected in FMD. 28 Patients with hereditary connective tissue dis­ orders may have aneurysms of major arteries similar to those of FMD. 27 Patients with EhlersDanlos syndrome have characteristic clinical signs such as joint laxity and increased skin elasticity. Neurofibromatosis may be associated with stenoses at the orifice of the renal, celiac, and superior mesenteric arteries and, less frequently, with narrowing of the abdominal aorta. 29 " 31 The proximal site of the arterial involvement, along with stigmas of neurofibromatosis of the skin and bones, which are almost always present, helps to distinguish this disease from FMD. Congenital abdominal coarctation also may be associated with proximal renal artery stenosis.

DIFFERENTIAL DIAGNOSIS The differential diagnosis of FMD includes arteriosclerosis, inflammatory vascular diseases such as Takayasu's arteritis, and vascular lesions of neurofibromatosis. Certain types of hereditary connective tissue diseases, such as Ehlers-Danlos syndrome, may angiographically mimic the aneurysmal type of FMD. 27

NATURAL HISTORY Progression of FMD has been confirmed on repeated angiograms in a substantial number of patients with renovascular disease. Meaney and co-workers32 reported that during an observation period of 6 months to 10 years, renovascular disease progressed in 36% of patients with atherosclerosis but in only 16% of those with FMD. In

Fig. 6. Cross-sectional photomicrographs of arteries with uncommon morphologic types of fibromuscular dysplasia. A, Perimedial (or periadventitial) fibroplasia. B and C, Intimal fibroplasia or intimal hyperplasia. (A, Hematoxylin and eosin; x40. B, Hematoxylin and eosin; x64. C, Elastic stain; x64.)

936

FIBROMUSCULAR DYSPLASIA

Mayo Clin Proc, October 1987, Vol 62

Fig. 7. A, Angiogram of intimal fibroplasia of left renal artery (confirmed histologically), showing high-grade stenosis at distal third of artery. B, Angiogram of periarterial fibroplasia, showing high-grade segmental stenosis in proximal part of right renal artery (histologically confirmed). C, Angiogram" of left internal carotid artery, demonstrating high-grade stenosis at level of C-2 vertebra, presumed to be attributable to intimal fibroplasia. (A and B, From Kincaid OW [ed]: Renal Angiography. Chicago, Year Book Medical Publishers, 1966, p 117. By permission.)

a Mayo Clinic series, during a mean observation period of 3 years, FMD of the renal arteries progressed in 35% of the patients. 33 Progression was more common in older patients with focal or tubular stenoses than in those with medial fibroplasia. Similarly, Kincaid and associates 34 and Pohl and Novick 35 observed progression of renovascular FMD in 36% and 38% of their patients, respectively; no patient had progression of the disease to occlusion of vessels. Development of hypertension has been noted in previously normo-

tensive patients with fibromuscular changes of the renal artery. 36 Spontaneous reversal of fibromuscular vascular lesions with reversal of hypertension may occur in very rare instances. 37 In patients with renovascular hypertension, the natural history of FMD may be influenced by the development of superimposed arteriosclerotic vascular lesions. Also, smoking is particularly common in patients with renovascular FMD and may affect the natural history of the disease. 38 In patients with cerebrovascular FMD, Corrin and colleagues 19 noted subsequent cerebral ischemic events after the initial angiogram in only 3 of 79 patients during a mean observation period of 5 years. Although this assessment of the natural history of the disease is clinical rather than angiographic, progression seems to be less pronounced in cerebrovascular than in renovascular FMD. In part, this outcome might be related to the high incidence of hypertension among patients with renovascular FMD.

Mayo Clin Proc, October 1987, Vol 62

PATHOGENESIS The cause of FMD remains unknown. Several hypotheses on the pathogenesis have been proposed. The most important concepts are (1) the humoral hypothesis, in which involvement of the female sex hormones has been suggested; (2) the mechanical hypothesis, in which the importance of trauma or repeated microtrauma has been emphasized; (3) the genetic hypothesis; and (4) the hypothesis of ischemia of the blood vessel wall. It is unlikely that all subtypes of FMD have the same underlying cause. Humoral Factors.—In most series of patients with FMD, a preponderance of female over male patients has been noted.1'4'6'7,14'15 Typically, women in the childbearing ages are affected. In one series of cerebrovascular incidents among patients taking oral contraceptives, radiologic features consistent with FMD were found in 18% of the patients. 39 Oral contraceptives may cause intimal hyperplasia. 40 During pregnancy, alterations of the vascular media and the elastic tissue may occur.41 Some smooth muscle cells and fibroblasts increase the production of collagen after exposure to estrogen in vitro. 42 In patients with FMD, however, gravidity and parity rates do not differ from those in the general population. Also, pregnancy does not seem to worsen the natural history of fibromuscular vascular lesions. 23 Mechanical Factors.—The blood vessels most commonly involved in FMD are the renal and internal carotid arteries, particularly on the right side, where the renal artery is longer. Nephroptosis is frequently associated with FMD of the right renal artery. 43 Cyclic stretching of arterial smooth cells results in an increase in production of collagen, hyaluronate, and chondroitin sulfate in vitro. 44 During extension and rotation of the head, the distal segment of the internal carotid artery is particularly prone to stretching and shearing around the bony margins of the uppermost cervical vertebrae. Hence, investigators have suggested that repeated stretching of this portion of the internal carotid artery during hyperextension of the vertebral column and of the renal artery during changes in posture and breathing, particularly if associated with nephroptosis, might at least partially explain the anatomic distribution of FMD. Experimental studies, however, revealed only minor histologic changes in response to stretching of the renal

FIBROMUSCULAR DYSPLASIA

937

artery. Trivial trauma involving the wall of the blood vessel might be an important triggering factor of medial dissection in the internal carotid artery. 46 Major trauma may cause occlusion of diseased arterial segments in previously asymptomatic patients. 47 Genetic Factors.—The importance of genetic factors in the pathogenesis of FMD is supported by the high incidence of the disease in some families and in Caucasians. Familial occurrence of FMD has been reported repeatedly. 48,49 In an analysis of 20 families in which at least one member had confirmed FMD, Rushton 50 found evidence of an inheritance pattern consistent with an autosomal dominant trait, with variable penetrance in 60% of the cases. In the patients with no family history of FMD, the vascular disease was considered a new mutation. In adult blacks, renovascular hypertension is much less frequent than in Caucasians and, if present, is caused by atherosclerotic lesions in three-fourths of the patients. 51 Ischemia.—Experimental occlusion of arterial vasa vasorum causes distinct morphologic changes of the vascular wall. 45,52 ' 53 In the media, the amount of extracellular connective tissue increases and myofibroblasts appear, particularly in the peripheral part. Electron microscopic studies of perimedial fibroplasia of the renal artery have revealed dense collagen fibers, some of which are continuous with smooth muscle cells. Smooth muscle cells may act as multipotential mesenchymatous cells capable of producing collagen and elastin. 54 On the basis of these data, investigators have concluded that a decreased blood supply to the vascular wall due to functional or morphologic occlusion of the vasa vasorum might be a primary event in the pathogenesis of FMD. The vasa vasorum of muscular arteries usually originate from branchings of parent vessels. 23 The extracranial internal carotid and external iliac arteries are frequently involved in FMD, and they also have fewer branches than other arteries of similar size. This difference could make them more susceptible to mural ischemia. In addition, it provides an explanation for involvement of the outermost part of the media in perimedial fibroplasia, a subtype of FMD, and for the absence of fibroplasia exclusively involving the inner media. Other Factors.—Some patients with pheochromocytoma have stenoses that resemble

938

FIBROMUSCULAR DYSPLASIA

strings of beads. 55,5 The high catecholamine levels associated with this endocrine tumor may cause or precipitate functional stenoses of large arteries and possibly the vasa vasorum. In some patients, stenotic lesions of the renal artery have disappeared after removal of the tumor. 56 Vascular lesions resembling those in FMD may also be associated with ergotamine intoxication and chronic use of methysergide. 57,58 Reversible renal artery stenosis and formation of a renal artery aneurysm presumably due to ischemia of the vascular wall have been noted in a patient taking ergotamine. 59 As in FMD, most patients with vascular complications during ergotamine therapy are women. 57 The incidence of smoking among patients with renovascular FMD is high. 38 Whether this factor is related to the pathogenesis of the disease process, however, remains unclear. Finally, FMD has been considered the end stage of some type of vasculitis or an Immunologie process. 60 Vascular changes ascribed to the rubella syndrome are similar to those in FMD.61 CLINICAL MANIFESTATIONS A N D MANAGEMENT OF FMD The clinical manifestations of FMD are determined by the arteries involved, the degree of vascular occlusion, and the presence or absence of a collateral circulation. Hence, the patients may be asymptomatic or may have signs and symptoms of vascular occlusive disease. Renovascular hypertension, transient ischemic attacks, and stroke are the most common clinical manifestations. Renovascular FMD. Clinical Aspects.—In comparison with patients who have arteriosclerotic renal artery stenosis, patients with renovascular FMD are younger, are more often female, and have a shorter duration of hypertension. 1,14 " 17 The right renal artery is more often involved in FMD than is the left.15 In some series, a family history of hypertension was uncommon in FMD, 14 whereas in others a high incidence of hypertension, stroke, or other vascular disease was found in relatives of the patients. 1,50 Impaired kidney function is uncommon in patients with renovascular FMD, even in those with bilateral renal arterial disease. 1 ' 6 ' 15,16 Symptomatic or asymptomatic extrarenal FMD may be present, particularly in patients with bilateral

Mayo Clin Proc, October 1987, Vol 62

renovascular involvement. 1,6 Renal artery aneurysms, either alone or in combination with stenoses, are a common finding in patients with renovascular FMD. 62,63 Renovascular D i s e a s e Versus Renovascular Hypertension.—Renovascular FMD causes hypertension if the stenosis is hemodynamically severe enough to induce renal ischemia. Renal ischemia and, in turn, activation of the reninangiotensin system are thought to be the primary pathophysiologic mechanisms involved in the persistence of high blood pressure in patients with renovascular hypertension, although the sympathetic nervous system also may contribute. 64 " 67 Distinguishing renovascular disease from renovascular hypertension is important. The presence of a severe stenosis (more than a 75% decrease in diameter) with a collateral circulation, a decrease in kidney size, and lateralization of secretion of renin toward the involved side in unilateral FMD is strongly indicative of a hemodynamically significant stenosis (Fig. 8). In unilateral FMD, a plasma renin activity (PRA) ratio (renal venous PRA of involved artery:renal venous PRA of uninvolved artery) of 1.5 or greater or a renin incremental index (renal venous [V] PRA - renal arterial [A] PRA)/(renal arterial [A] PRA), or (V - A)/A, of more than 0.48 is consistent with significant renal artery stenosis 66,67 (Fig. 9). Renal venous renin determinations may be useful in the workup of unilateral renovascular hypertension, although the test result may be false-negative in many patients, particularly those with FMD. 66 " 70 Sodium depletion enhances the sensitivity of the test. 71 A continuous bruit may be heard in about twothirds of these patients. 14 Complications.—Renal arterial aneurysms may cause hypertension either through associated stenoses, dissection, or compression of arteries or renal tissue by large aneurysms or through peripheral emboli originating in the aneurysm and causing local renal ischemia.62,63,72,73 Rupture of fibromuscular aneurysms is very rare, even in patients with hypertension. 62 Rarely, rupture of fibromuscular aneurysms into a renal vein causes renal arteriovenous fistulas. 74,75 Although renal arteriovenous fistulas are controversial as a cause of hypertension, at least in some patients they may be related to high blood pressure through asso-

Mayo Clin Proc, October 1987, Vol 62

FIBROMUSCULAR DYSPLASIA

939

Fig. 8. Distinguishing renovascular disease from renovascular hypertension is important. A, Severe renal arterial narrowing (more than 75%), presence of collateral vessels, and decreased kidney size strongly suggest hemodynamically significant stenosis. B, After dilation of stenosis, collateral circulation disappeared. (From Lüscher TF, Greminger P, Kuhlmann U, Largiader F, Schneider E, Pouliadis G, Siegenthaler W, Vetter W: Fibromuskuläre renovaskuläre Hypertonie: Vergleich von Operation, transluminaler Dilatation und medikamentöser Therapie. Schweiz Med Wochenschr 115:146-153, 1985. By permission of Schwabe & Co. AG.)

ciated stenoses, peripheral emboli, or compression of neighboring arteries. In patients with FMD, dissection of the renal artery seems to be rarer than the occurrence of dissection in the cerebrovascular circulation. Most of these patients have hypertension. Dissection seems to be most common in young male patients with bilateral renal FMD. 63 Renal infarction is a potential complication of renovascular FMD, particularly if a dissection or large aneurysm is present. Clinically, renal infarction may cause abdominal or flank pain with or without nausea, vomiting, and transient fever.73 Proteinuria, hematuria, and elevations of lactic dehydrogenase and serum glutamicoxaloacetic transaminase also may occur. Not all patients with renal infarction have hypertension. 72 Selective samplings of renin in the

branches of the renal vein may be useful in detecting local renin oversecretion in hypertensive patients with renal infarction. 62 Management.—Treatment of renovascular disease may be indicated to normalize blood pressure or to preserve renal function. In FMD, in contrast to arteriosclerotic renovascular disease, preservation of renal function is rarely a primary decision for treatment. Nephrectomy was the first curative intervention in renovascular hypertension. 2 Later, surgical vascular reconstruction became available. In 1978, Griintzig and associates 76 reported the first successful percutaneous transluminal dilation of a renal artery stenosis. Since then, this new method has been used in a growing number of patients. 1,16 ' 77 Moreover, in recent years, potent antihypertensive drugs have been developed.78"80

940

FIBROMUSCULAR DYSPLASIA

A

|VC

Aorta

Mayo Clin Proc, October 1987, Vol 62

B

(VA > 8

^^^^^HL...

<"=28>

A

i

-i

.

■■'■

· \

p<0.001

(V_A, ,

A

r 8 :■

20 -

- 2.0

%

Ä

1.5 -

Äv

1.0 -

β,, θΙ, βίη PRA r a t i o PRA - ^ Λ Ιright κ Γrenal ; vein

0 5 -

.™ ■

(V-A) A

PRA renal vein-PRA IVC PRA IVC

0 -

- 1.5

STENOTIC SIDE

/

- 1.0

-0.5

^

-

0

NON STENOTIC SIDE

Fig. 9. A, Diagram showing anatomic sites (white circles) for measurement of plasma renin activity (PRA). A = arterial plasma renin activity (for practical purposes, plasma renin activity in inferior vena cava [IVC] is used). V - plasma renin activity in renal vein. B, Lateralization of renin secretion in 28 patients with unilateral renal artery stenosis supports functional significance of this disorder. (A, Modified from Liischer TF, Essandoh LK, Lie JT, Hollier LH, Sheps SG.27)

Hence, three therapeutic approaches are currently available for the management of renovascular hypertension. Surgical vascular reconstruction and nephrectomy are the most extensively studied techniques with the longest follow-up periods1,65,81~92 (Table 1). The surgical techniques include revascularization with an autogenous vein or artery or with a synthetic graft, operative arterial dilation, and autotransplantation. Today, nephrectomy is performed only in patients in whom revascularization has failed or is technically impossible or in those who have a nonfunctioning kidney. In patients treated surgically, the cure rates are higher and the mortality is lower with FMD than with atherosclerotic renovascular disease. 16 ' 82,92 The cure rates in FMD range from 38 to 85%. From 12 to 45% of the patients have improvement

postoperatively (Table 1). In a cooperative study of renovascular hypertension, the complication rate was 13% and the surgical mortality was 3.4%.93 In recent years, the associated surgical mortality and morbidity have decreased, particularly in older patients. 94 Surgical mortality is closely related to the presence of coronary artery disease and impaired kidney function. 93 Extracorporeal or ex vivo surgical techniques allow repair of FMD involving the branches and segmental arteries, which is particularly common in medial and perimedial fibroplasia 95 (Fig. 3 A and 5). Percutaneous transluminal angioplasty of the renal artery (PTRA) is a nonsurgical technique that produces dilation of localized renal artery stenoses by means of a balloon catheter 76,77 (Fig. 8). String-of-beads stenoses are easy to di-

Mayo Clin Proc, October 1987, Vol 62

FIBROMUSCULAR DYSPLASIA

Table 1.—Results of Renovascular Surgical Treatment or Nephrectomy in Patients With Fibromuscular Dysplasia of the Renal Arteries and Hypertension* Blood pressure response (%) Follow-up Operative (mo) Authors N mortality (%) Year Cured Improved Unimproved Foster et al81 1973 44 >6 72 2.3 24 4 7-14 Hunt and Strong65 1973 58 67 NR 7 26 12 3.4 29 Franklin et al14'82'93 1975 151 58 13 6-168 1976 Buda et al83 42 10 76 14 lt >12 1978 27 59 22 Novick et a T t 19 3.7 85 Bergentz et al 10 NR 1979 40 66 24 0 4 6-60 Lankford et al86 1979 31 56 40 4 87 NR Whelton et al 1979 15 40 NR 24 NR 33 Lawrie et al88 43 24 49.3 1980 113 1.8 (1-240) 89 Zuber et al NR NR 1980 25 38 37 25 Lüscher et al1 1986 3 52 45 30 0 33 2 32 Stoney et al 9 ^ 1981 77 66 67 0 12 3 >6 Stanley et al91 0 1982 85 34 P 39 6 NR 0 144 A 55

941

Complication rate (%) 32.8t NR 13.3t NR 7.4 7.5t NR NR NR NR 11 5.2 NR NR

*A = adult patients; NR = not reported; P = pediatric patients. tFibromuscular and atherosclerotic renal artery stenoses analyzed collectively. JPediatric patients only (1 to 18 years old). §Aortorenal autografts only.

late, even with low balloon pressures. 96 Focal fibromuscular stenoses, such as intimal or periarterial fibroplasia, are much more resistant to dilation. In some patients with incomplete initial dilation, the response to PTRA is delayed and the lesions have been completely healed at follow-up.96 Currently, the indications for PTRA are basically the same as those for renovascular surgical treatment. The cure rates for PTRA in patients with FMD range from 25 to 85%1'16'77'92'97"104 (Table 2). With one exception among the reported studies, about half to two-thirds of the patients

were cured after PTRA. These cure rates are comparable to those after surgical intervention, although the follow-up periods are shorter for PTRA than for surgical treatment. The longlasting effects of PTRA have been substantiated for up to a 5-year period. 77 The results of both surgical treatment and PTRA are best in patients with unilateral FMD, poorer in those with bilateral involvement, and poorest in those with systemic FMD. 1 The reported complication rates of PTRA range from 0 to 17% (Table 2). The primary success rate and the complication rate of PTRA are closely

Table 2.—Results of Percutaneous Transluminal Angioplasty of the Renal Artery in Patients With Fibromuscular Renovascular Disease and Hypertension* Primary Blood pressure response (%) success Follow-up Complication rate (%) Cured Improved Unimproved (mo) rate (%) Authors Year N 66 79 44 48 1980 Schwarten et al 97 t >6 17 NR 11 82 44 56 Colapinto et al98 1982 1-36 NR 99 NR 6 100 83 17 Mahler et al 1982 22 (6-39) 0 21 NR 48 47 5 Geyskes et al100 1983 12-48 NR 27 59 33 Sos et al16 1983 8 16 (4-40) 7.4 87 101 27 37 63 Tegtmeyer et al 1984 NR 24 (1-60) lit 94t 103 13 67 25 Millan et al 1985 8 37 (10-73) 7.7 86 15 85 15 Miller et al104 1985 NR 100 >6 3t 20 25 60 Martin et al102 1985 15 100 11 3-39 77 22 50 32 Kuhlmann et al 1985 18 0 91 22 (1-65) 92 26 58 35 Grim et al 1986 NR NR 26 (1-60) *NR = not reported. tFibromuscular and atherosclerotic renal artery stenoses analyzed collectively.

942

FIBROMUSCULAR DYSPLASIA

Mayo Clin Proc, October 1987, Vol 62

related to the experience of the center at which artery stenosis or occlusions and in patients with the technique is performed and the extension of a solitary kidney and renovascular disease. 1,109 FMD into the renal branch arteries. 1,105 The most Hence, in these patients, converting enzyme infrequent complications are hematomas at the hibitors are contraindicated. puncture site—most commonly the femoral artery Which therapeutic modality should be chosen and sometimes the brachial artery—or acute for a specific patient? To date, no controlled, renal failure associated with the use of contrast randomized trial comparing the various theramaterial. Acute renal failure after PTRA usually peutic approaches available for patients with occurs in patients with impaired kidney function renovascular hypertension has been performed. or a solitary functioning kidney. Particularly in Surgical revascularization clearly is the bestyoung patients with FMD, arterial spasm may documented therapy. The advantages of PTRA occur during the angioplasty procedure. 106 Major are its relative noninvasiveness, lack of need for complications of PTRA that necessitate im- general anesthesia, low associated mortality and mediate surgical intervention are uncommon; ex- complication rates, and short hospitalization peamples are renal artery perforation, dissection, riod. In addition, unsuccessful PTRA does not and thrombotic occlusion. Ruptures occurring preclude a later renovascular surgical procedure. hours after PTRA and characterized by per- In older studies, surgical intervention seemed to sistent flank pain have been reported in only two achieve a better long-term survival of patients patients. 107 No mortality has been reported in with renovascular hypertension than did medical association with PTRA in patients with FMD. therapy. 65 With modern antihypertensive drugs, From a pathophysiologic point of view, anti- however, the blood-pressure-lowering effect of hypertensive drugs used in renovascular hyper- medical therapy may be as good as that with tension should interfere with the renin- surgical treatment. Drug side effects and low angiotensin system by either suppressing the patient compliance may jeopardize the long-term secretion of renin or inhibiting the converting effects of medical therapy. 110 Also, a potential enzyme. /5-Adrenergic blocking agents are effec- risk of medical therapy is progression of the tive in renovascular hypertension. 78 Patients arterial disease, leading to reduction in renal with renovascular hypertension respond better to function. 33 Cerebrovascular Fibromuscular Hyperconverting enzyme blockade than do those with essential hypertension of comparable severity, plasia. Clinical Aspects.—In 1965, the first both under acute conditions and during long-term histologically proven case of FMD of the carotid artery was reported 4 (Fig. 3 B and 4). Cerebrotherapy 79108 (Fig. 10). With captopril therapy, the mean blood pres- vascular FMD may either occur incidentally or sure is lower and the percentage of patients with be related to clinical symptoms such as ischemic excellent blood pressure control is higher among or hemorrhagic stroke, transient ischemic atthose with renovascular hypertension than those tacks, amaurosis fugax, and syncope.5,6,18,19,111 with severe essential hypertension. The potential Not all symptoms found in patients with FMD disadvantages of long-term therapy with cap- are necessarily related to this disease. Asymptomtopril are serious side effects, usually occurring atic FMD of cerebral arteries has been found after administration of high dosages only. The in patients undergoing angiography for intraside effects of captopril include pruritus, rashes, cranial mass lesions or other reasons. 18 Symptoms can be related to stenotic lesions or ocloss of taste, proteinuria, and leukopenia. 79 Non-sulfhydryl-containing angiotensin-convert- clusions of major cephalic arteries, rupture ing enzyme inhibitors, such as enalapril, proved of intracerebral aneurysms, or cerebral emmore effective than standard triple therapy for boli that originate from small intravascular renovascular hypertension in one reported thrombi in string-of-beads stenoses or aneurysstudy. 80 The compound seems to be associated mal FMD.5,6,111,112 The last-named possibility with better tolerance and safety, although the may in part explain why in symptomatic patients clinical experience is somewhat more limited the fibromuscular changes at angiography may than that with captopril. Converting enzyme in- be less pronounced than they seem clinically and hibitors may cause dramatic increases in plasma occlusions are relatively rare except in patients creatinine levels in patients with bilateral renal with spontaneous dissections. 113 Bilateral lesions

Mayo Clin Proc, October 1987, Vol 62

FIBROMUSCULAR DYSPLASIA

ACUTE RESPONSE

B

CHRONIC

( 25 mg captopril orally)

Essential Hypertension

250r

100

n-30 302925 19 18 II 9

943

RESPONSE Renovascular Hypertension 20202017 II II II 8

80

Φ 60 (0

c o a. « 40 20

15

30

60

120

Time, minutes a * essential hypertension, n-39 ■ •renovascular hypertension,n-22

STT I, I 3 6 9 12 18 '4

STT I, I 3 6 9 12 18 '4

Time, months

■ ■ diastolic blood pressures 95 mmHg a * diastolic blood pressure 96-105mm Hg D > diastolic blood pressure > 105 mmHg

Fig. 10. Short- and long-term effects of captopril therapy in lowering blood pressure in essential and renovascular hypertension. A, Note more pronounced decrease of blood pressure in renovascular than in essential hypertension shortly after administration of captopril. (Asterisks = groups significantly different, ί"<0.05.) Β, During long-term treatment of severe hypertension, the number of patients with excellent blood pressure response is substantially higher among those with renovascular than those with essential hypertension. STT = standard triple therapy. (Modified from Havelka J, Vetter H, Studer A, Greminger P, Liischer T, Wollnik S, Siegenthaler W, Vetter W/ 9 By permission of Reed Publishing.)

and fibromuscular changes in multiple cephalic arteries are common.1,5,6,18 The percentage of symptomatic patients with cerebrovascular FMD varies considerably in the literature. 1,5,6,18,19'114 Most patients complain of minor symptoms, such as headache, tinnitus, vertigo, audible bruits, or fatigue. The frequent occurrence of headaches has been related to vasoactive substances (such as serotonin or thromboxane A 2 ) released from aggregating platelets activated on vascular lesions or by turbulent flow.5 Houser and associates 18 and Corrin and colleagues 19 noted major symptoms, such as tran­

sient ischemic attacks, strokes, and subarachnoid bleeding, in approximately a third of their patients, whereas in a series reported by Mettinger and Ericson, 5 most patients had major symptoms related to FMD. Because patients un­ dergoing angiography are a selected group, the overall incidence of major symptoms in patients with cerebrovascular FMD is probably consider­ ably lower. Horner's syndrome and paresis of cranial nerves IX through XII (Collet-Sicard syn­ drome) are rare symptoms related to berry aneurysms that exert pressure on neighboring nerves. 5,114 The prognosis for symptomatic pa-

944

FIBROMUSCULAR DYSPLASIA

tients with cerebrovascular FMD seems to be excellent; only a minority have progression of the disease or symptoms over several years. 19,113 Complications.—A potentially serious complication of cerebrovascular FMD is spontaneous dissection of the arterial wall, usually of the internal carotid artery. 46,115 " 119 Dissections of the vertebral artery or the superior cerebellar artery are less common.45,120"123 Rarely, dissections are associated with carotid-cavernous sinus fistulas.124 Early clinical manifestations of spontaneous dissection of the internal carotid artery are sudden onset of headache or neck pain, blurred vision, or Homer's syndrome. In some patients, the symptoms appear during physical exercise, after abrupt head movements, or after neck trauma. Signs of transient or permanent cerebral ischemia (for example, hemiplegia or aphasia) are present in all patients. Among patients with multivessel involvement, the mortality is high.46,118,121,122 Spontaneous dissections of the vertebral artery seem to be associated with a more favorable outcome than are dissections of the internal carotid artery. 122,123 The diagnosis of spontaneous carotid artery dissection depends on the detection of long, irregular filling defects ("string sign") on angiograms. Because the lesions typically extend to or into the carotid canal, surgical intervention is difficult. Usually, FMD vascular stenoses are present in other arteries. Spontaneous arteriovenous fistulas between the internal carotid artery and the cavernous sinus or the vertebral artery and the paravertebral veins also have been detected in patients with cerebrovascular FMD. 124 An association between FMD and intracranial aneurysms was first suggested by Palubinskas and Newton. 125 Subsequently, an incidence of intracranial aneurysms as high as 51% in patients with FMD was noted by others.1,5,8,18,126"128 Some patients have multiple aneurysms. Most aneurysms are located in the intracranial portion of the internal carotid artery and the middle cerebral artery. In a review of 284 patients with cerebrovascular FMD published in the literature, 111 intracranial aneurysms were found in 21%. Two-thirds of these patients had multiple intracranial aneurysms. Because most patients with FMD in a location other than the cerebrovascular bed usually do not undergo cerebral angiography, the actual incidence might be even higher. In contrast, in autopsy series the inci-

Mayo Clin Proc, October 1987, Vol 62

dence of intracranial aneurysms is only 0.5 to 4.9%111,129 Hence, investigators have speculated that a subset of the patients with intracranial aneurysms may in fact have FMD. Aneurysms of the internal carotid artery and middle cerebral artery are twice as common in female patients as in male patients and are likely to be associated with aneurysms elsewhere. In contrast, aneurysms of the anterior cerebral artery most commonly occur alone and in male patients. 111 Management.—The management of cerebrovascular FMD depends on the severity of the symptoms and the extension of the fibromuscular changes. Before a therapeutic modality is chosen, the relatively benign natural history of the disease should be kept in mind. 19 Surgical intervention should be reserved for patients with evidence of progressive cerebral ischemia. Various surgical techniques have been used for cerebrovascular FMD: (1) resection of the vascular lesion and primary anastomsis or interposition of a venous graft, 130 (2) patch angioplasty in conjunction with graduated intraluminal dilation, (3) intraluminal operative graduated dilation with use of Garrett dilators or Fogarty catheters, 130 " 138 and (4) bypass between the carotid artery and the middle cerebral artery 139 (Table 3). Today, most surgeons consider graduated intraluminal dilation the method of choice in FMD of the extracranial arteries, provided the lesion is surgically accessible. In all reported series, the operative mortality has been zero, the postoperative morbidity has been low, and symptoms have rarely recurred (Table 3). Although dissection is a common spontaneous complication of cerebrovascular FMD, it seldom is a complication of this technique. In surgically inaccessible lesions that extend into the intracranial portions of the carotid artery, bypass between the external carotid artery and the middle cerebral artery has been used. 139 Percutaneous transluminal angioplasty has been successfully performed in a few patients with FMD of the internal carotid artery. 140 " 144 In 11 of the 12 patients described in published reports, the angiographic and clinical results were excellent. Neurologic complications occurred in one patient who had intimal dissection after angioplasty. 145 Antiplatelet agents have been used as medical therapy for cerebrovascular FMD. Of 19 patients with a mean follow-up period of almost 2 years,

Mayo Clin Proc, October 1987, Vol 62

FIBROMUSCULAR DYSPLASIA

945

Table 3.—Results of Surgical Treatment of Symptomatic Fibromuscular Dysplasia of the Cerebral Arteries* Clinical Operative Follow-up Operations Operative Surgical results Year N (no.) Authors mortality morbidity technique (mo) Good 1967 1 1 1, transient Resection and 8 Ehrenfeld et al131 0 hypoglossal end-to-end paresis anastomosis 132 2, transient Morris et al Good 1968 8 10 0 GID 2-48 hypoglossal paresis 15 1, carotid artery 25, excellentGID Stanley et al133 1974 NR NR NR thrombosis; 2, good; 2, fairResection 10 limited dissecpoor Angioplasty 3 tions of ICA with graft 7, TIA; 2, neuroExcellent in 1979 68 96 Effeney et al130 0 6-48 GID most; 1, neurologic deficits logic deficit; 2, SAH 3, strokes; 8, Excellent in Effeney et al134 1980 79 118 0 6-108 GID TIA most; 1, occlusion; 2, SAH; 2, recurrences Collins et al135 1981 18 18 None Good 0 12-68 GID 1, occlusion of Good in most; 2, GID Starr et al136 1981 25 36 0 6-96 occlusion of ICA 2 Resections, ICA; 1, recurcombinations rence at contralateral ICA 137 Danza et al None 1983 9 0 GID 9 NR Good 1, transient GID, intraoperaLevien et al138 1984 6 0 8 Good 4-12 hemiparesis tive angioplasty *GID = graduated intraluminal dilation; ICA TIA = transient ischemic attack.

"internal carotid artery; NR = not reported; SAH = subarachnoid hemorrhage;

only 2 had recurrent symptoms during antiplatelet therapy. 146 Patients with spontaneous dissection of the carotid artery have been treated with surgical procedures, 119 with anticoagulants, 116 ' 122 or with antiplatelet drugs. 115 ' 119 Recanalization of the dissected area has been reported in a considerable number of patients treated with heparin 116,122,123 whereas acetylsalicylic acid has been less effective.115,119 FMD of the Visceral Arteries.—Typical locations of FMD in the visceral arteries are the celiac artery, the superior and inferior mesenteric arteries, and the hepatic and splenic arteries.1,6"8 Fibromuscular lesions of the hepatic and splenic arteries are relatively rare and usually are incidental findings at angiography. 7,8 Most commonly, the celiac trunk or the superior mesenteric artery is involved. String-of-beads stenoses are less common in these vascular beds than in the renovascular or cerebrovascular areas. Most often, tubular stenoses are found in these arteries (Fig. 11 A), but aneurysmal forms of FMD may

be seen as well.6,9 In symptomatic patients, the classic triad indicative of occlusive intestinal arterial disease is postprandial abdominal pain, weight loss, and an epigastric bruit. In patients with concomitant renovascular disease, a bruit may also be related to a renal artery stenosis. Because of the development of collateral circulation through the inferior mesenteric artery (Riolan's anastomosis) (Fig. 11 B) or between the celiac branches and the superior mesenteric artery, the intestine is relatively resistant to ischemia unless at least two of the major arteries are obstructed. Mesenteric infarction is extremely rare in FMD. 6,147 Single-vessel FMD and clinical symptoms relieved by vascular surgical intervention, although very rare, have been reported. 147 Ischemic proctitis due to FMD of the superior rectal artery is exceedingly rare. 148 The importance of stenotic lesions that cause no clinical symptoms is questionable. In symptomatic patients, surgical revascularization is necessary. Recently, percutaneous trans-

946

FIBROMUSCULAR DYSPLASIA

Mayo Clin Proc, October 1987, Vol 62

Fig. 11. A, Fibromuscular dysplasia of superior mesenteric artery. Note tubular smooth appearance of stenosis (arrow), which spares orifice of artery. B, Injection into inferior mesenteric artery shows retrograde filling of distal superior mesenteric artery through marginal artery of colon (Riolan's anastomosis). (From Lüscher T, Vetter H, Studer A, Kuhlmann U, Pouliadis G, Schmidt I, Siegenthaler W, Vetter W.6 By permission of Springer-Verlag.)

luminal angioplasty of the intestinal arteries was successfully performed in a small number of patients. 149 ' 150 FMD of the Subclavian and Axillary Arteries.—Subclavian FMD is as frequent as FMD of the intestinal arteries. 1 ' 6,151 This vascular bed seems particularly frequently involved in patients with systemic FMD. If hemodynamically significant, subclavian FMD may lead to a difference in blood pressure between the right arm and the left arm. Severe lesions may cause weakness of the arm, paresthesias, and, eventually, claudication during exercise.6,151,152 If the proximal part of the artery is occluded or severely obstructed, a subclavian steal syndrome with dizziness and other symptoms of cerebrovascular insufficiency may develop during arm exercise. Under these circumstances, blood flow in the ipsilateral vertebral artery is reversed. Most pa-

tients with subclavian FMD have surprisingly few symptoms, even with bilateral stenoses or occlusions. 6 Often, patients with subclavian FMD have hypertension because of concomitant renovascular disease. 1,6,152 If the blood pressure is measured in the involved arm in asymptomatic patients, hypertension may be underestimated or overlooked, particularly in patients with bilateral subclavian disease. FMD of the axillary and brachial arteries is extremely rare. 7,153 A vascular operation should be considered only in patients with symptoms. Percutaneous transluminal angioplasty has been used successfully in patients with stenosis of the subclavian or innominate artery. 154 The management of patients with subclavian artery aneurysms is controversial, particularly if no symptoms are present. In arteriosclerotic aneurysms at this location, complications include shoulder pain

Mayo Clin Proc, October 1987, Vol 62

(from an expanding aneurysm), rupture, peripheral microemboli, and arterial occlusion.152 These complications, however, probably are much less common in FMD than in atherosclerosis. The advantages of surgical management are definitive repair and low associated morbidity and mortality. FMD of the Iliac Arteries.—Although probably not that rare, FMD of the iliac arteries has been reported in only 24 patients.1'6'7'60'153'155"163 The external iliac arteries were almost exclusively involved in those patients. Rarely, the common iliac, deep femoral, popliteal, tibial, and peroneal arteries were affected as well.6'153 Most patients were 50 years old or older. Fourteen of the 24 patients had symptoms. Intermittent claudication and coldness of the lower extremity were the most common complaints. Two patients had peripheral microembolism, evidenced by pain and cyanosis in the toes. 61,159 Dissecting aneurysms of the external iliac artery are rare and are manifested by acute severe pain in the inguinal region. 163 Surgical revascularization may be necessary in patients with symptoms. Of 11 patients who underwent operation, 9 had excellent results, and 2 had progressive disease that necessitated reoperation or amputation of the extremity. Use of percutaneous transluminal angioplasty in patients with FMD of the iliac arteries has not been reported thus far; however, the results of angioplasty in atherosclerotic occlusive disease of the iliac arteries have been excellent.164 Most likely, this procedure would be equally successful in patients with FMD of the iliac arteries. FMD of Large Coronary Arteries.—Coronary artery FMD is extremely rare. In 1965, Hill and Antonius 11 reported morphologically questionable examples of coronary FMD in two women, 73 and 26 years old. Subsequently, James and Marshall 165 described two patients, both of whom died suddenly, who had multifocal narrowing of the sinus node artery with histologic changes that the authors considered were consistent with intimal hyperplasia. We noted a similar case in a young girl who died suddenly. 1 Whether these vascular changes represent the same entity as intimal hyperplasia in other vascular beds is still controversial. 22,23 Although extremely rare, classic types of true medial FMD with dissections do occur in large coronary arteries. 26

FIBROMUSCULAR DYSPLASIA

947

SYNDROMES A N D DISEASES ASSOCIATED WITH FMD Coarctation of the Aorta.—Coarctation of the thoracic aorta is 4 or 5 times more frequent in male than in female patients. In contrast, coarctation of the abdominal aorta is evenly distributed between the sexes or, as in FMD, has a slight preponderance in females.10,166"168 An association of FMD of the renal arteries and coarctation of the abdominal aorta has been observed in seven patients. 6,10,166 ' 167 In five of them, histologic findings in the renal arteries or the coarctation (or both) were compatible with FMD. Thus, the two lesions may coexist or may even represent the same vascular disease in a subgroup of patients with abdominal coarctation. In the other two patients, coarctation of the thoracic aorta was associated with FMD of the renal artery in one and of the internal carotid artery in the other.168,169 In patients with abdominal coarctation, neurofibromatosis should be carefully excluded29"31 (see "Differential Diagnosis"). Abdominal coarctation may be infrarenal, suprarenal, or both; infrarenal coarctation is more common. Suprarenal abdominal and thoracic coarctation is associated with hypertension. 6 Pheochromocytoma.—Rarely, pheochromocytomas occur together with a renal artery stenosis, invariably involving the homolateral kidney. 56,170 In most cases, the stenosis has been attributed to a catecholamine-induced vasospasm, tumoral compression of the artery, or atherosclerosis. The coexistence of histologically proven renovascular FMD and a pheochromocytoma has been reported repeatedly. 55,171 Whether this association of the two disorders in these patients is causal or coincidental is unclear. Investigators have speculated that elevated catecholamine levels in patients with pheochromocytoma could cause morphologic changes of the arterial wall comparable to those of FMD through spasms of the vasa vasorum (see "Pathogenesis"). The overall low frequency of this vascular lesion in patients with pheochromocytoma, however, undermines this interpretation. Alport's Syndrome.—Alport's syndrome is the most common type of hereditary nephritis that causes end-stage renal disease. 172 The syndrome is associated with deafness and, in variants of the disease, with ocular defects, abnormal thrombopoiesis, and aminoaciduria. A link between FMD and Alport's syndrome has been

948

FIBROMUSCULAR DYSPLASIA

suggested, because renal biopsy specimens from patients with Alport's syndrome show vascular intimal thickening in small intrarenal arteries. 172 Whether these vascular changes are part of the same disease entity as FMD, however, remains unclear. Severe hypertension is unusual in patients with hereditary nephritis. If it is present, a search for correctable causes of hypertension seems necessary.

REFERENCES 1. Lüscher TF, Keller HM, Imhof HG, Greminger P, Kuhlmann U, Largiader F, Schneider E, Schneider J, Vetter W: Fibromuscular hyperplasia: extension of the disease and therapeutic outcome; results of the University Hospital Zurich Cooperative Study on Fibromuscular Hyperplasia. Nephron 44 (Suppl 1):109-114,1986 2. Leadbetter WF, Burkland CE: Hypertension in unilateral renal disease. J Urol 39:611-626,1938 3. McCormack LJ, Hazard JB, Poutasse EF: Obstructive lesions of the renal artery associated with remediable hypertension (abstract). Am J Pathol 34:582, 1958 4. Connett MC, Lansche JM: Fibromuscular hyperplasia of the internal carotid artery: report of a case. Ann Surg 162:59-62, 1965 5. Mettinger KL, Ericson K: Fibromuscular dysplasia and the brain: observations on angiographic, clinical and genetic characteristics. Stroke 13:46-52,1982 6. Lüscher T, Vetter H, Studer A, Kuhlmann U, Pouliadis G, Schmidt I, Siegenthaler W, Vetter W: Extrarenaler Gefässbefall bei fibromuskulär bedingter renovaskulärer Hypertonie. Klin Wochenschr 58:493-500, 1980 7. Garrett HE, Hodosh S, DeBakey ME: Fibromuscular hyperplasia of the left axillary artery. Arch Surg 94:737738,1967 8. Wylie EJ, Binkley FM, Palubinskas AJ: Extrarenal fibromuscular hyperplasia. Am J Surg 112:149-154, 1966 9. Patchefsky AS, Paplanus SH: Fibromuscular hyperplasia and dissecting aneurysm of the hepatic artery. Arch Pathol 83:141-144,1967 10. Connolly JE: Fibromuscular hyperplasia of the abdominal aorta. J Cardiovasc Surg (Torino) 19:563-566, 1978 11. Hill LD, Antonius JI: Arterial dysplasia: an important surgical lesion. Arch Surg 90:585-595, 1965 12. Rosenberger A, Adler 0 , Lichtig H: Angiographic appearance of the renal vein in a case of fibromuscular hyperplasia of the artery. Radiology 118:579-580, 1976 13. Youngberg SP, Sheps SG, Strong CG: Fibromuscular disease of the renal arteries. Med Clin North Am 61:623641, May 1977 14. Simon N, Franklin SS, Bleifer KH, Maxwell MH: Clinical characteristics of renovascular hypertension. JAMA 220:1209-1218,1972 15. Lüscher TF, Vetter H, Studer A, Pouliadis G, Kuhlmann U, Glänzer K, Largiader F, Hauri D, Greminger P, Siegenthaler W, Vetter W: Renal venous renin activity in various forms of curable renal hypertension. Clin Nephrol 15:314-320, 1981

Mayo Clin Proc, October 1987, Vol 62

16. Sos TA, Pickering TG, Sniderman K, Saddekni S, Case DB, Silane MF, Vaughan ED Jr, Laragh JH: Percutaneous transluminal renal angioplasty in renovascular hypertension due to atheroma or fibromuscular dysplasia. N Engl J Med 309:274-279,1983 17. Heffelfinger MJ, Holley KE, Harrison EG Jr, Hunt JC: Arterial fibromuscular dysplasia studied at autopsy (abstract). Am J Clin Pathol 54:274, 1970 18. Houser OW, Baker HL Jr, Sandok BA, Holley KE: Cephalic arterial fibromuscular dysplasia. Radiology 101:605-611,1971 19. Corrin LS, Sandok BA, Houser OW: Cerebral ischemic events in patients with carotid artery fibromuscular dysplasia. Arch Neurol 38:616-618, 1981 20. Claiborne TS: Fibromuscular hyperplasia: report of a case with involvement of multiple arteries. Am J Med 49:103-105, 1970 21. Chen W-Y, Lin J-T, Hsieh B-S, Yen T-S, Su C-T, Tang S-S, Lien W-P: Renal and extrarenal arterial fibromuscular hyperplasia with hypertension. NZ Med J 96:846-848, 1983 22. Harrison EG Jr, McCormack LJ: Pathologic classification of renal arterial disease in renovascular hypertension. Mayo Clin Proc 46:161-167, 1971 23. Stanley JC, Gewertz BL, Bove EL, Sottiurai V, Fry WJ: Arterial fibrodysplasia: histopathologic character and current etiologic concepts. Arch Surg 110:561-566, 1975 24. McCormack LJ, Poutasse EF, Meaney TF, Noto TJ Jr, Dustan HP: A pathologic-arteriographic correlation of renal arterial disease. Am Heart J 72:188-198, 1966 25. Osborp AG, Anderson RE: Angiographic spectrum of cervical and intracranial fibromuscular dysplasia. Stroke 8:617-626, 1977 26. Lie JT, Berg KK: Isolated fibromuscular dysplasia of the coronary arteries with spontaneous dissection and myocardial infarction. Hum Pathol 18:654-656, 1987 27. Lüscher TF, Essandoh LK, Lie JT, Hollier LH, Sheps SG: Renovascular hypertension: a rare cardiovascular manifestation of the Ehlers-Danlos syndrome. Mayo Clin Proc 62:223-229, 1987 28. Sheps SG, McDuffie FC: Vasculitis. In Allen-BarkerHines Peripheral Vascular Diseases. Fifth edition. Edited by JL Juergens, JA Spittell Jr, J F Fairbairn II. Philadelphia, WB Saunders Company, 1980, pp 493-553 29. Reubi F: Neurofibromatose et lesions vasculaires. Schweiz Med Wochenschr 75:463-465, 1945 30. Halpern M, Currarino G: Vascular lesions causing hypertension in neurofibromatosis. N Engl J Med 273:248-252,1965 31. Allan TNK, Davies ER: Neurofibromatosis of the renal artery. Br J Radiol 43:906-908, 1970 32. Meaney TF, Dustan HP, McCormack LJ: Natural history of renal arterial disease. Radiology 91:881-887,1968 33. Sheps SG, Kincaid OW, Hunt JC: Serial renal function and angiographic observations in idiopathic fibrous and fibromuscular stenoses of the renal arteries. Am J Cardiol 30:55-60, 1972 34. Kincaid OW, Davis GD, Hallermann FJ, Hunt JC: Fibromuscular dysplasia of the renal arteries: arteriographic features, classification, and observations on natural history of the disease. Am J Roentgenol 104:271-282, 1968 35. Pohl MA, Novick AC: Natural history of atherosclerotic and fibrous renal artery disease: clinical implications. Am J Kidney Dis 5:A120-A130, 1985 36. Felts JH, Whitley NO, Johnston FR: Progression of medial fibroplasia of the renal artery and the development of renovascular hypertension. Nephron 24:89-90, 1979

Mayo Clin Proc, October 1987, Vol 62

37. Siegler RL, Miller FJ, Mineau DE, Moatamed F: Spontaneous reversal of hypertension caused by fibromuscular dysplasia. J Pediatr 100:83-85, 1982 38. Nicholson JP, Teichman SL, Alderman MH, Sos TA, Pickering TG, Laragh JH: Cigarette smoking and renovascular hypertension. Lancet 2:765-766, 1983 39. Hardy-Godon S, Fredy D, Chodkiewicz JP, Perez J, Bories J: Angiography of cerebrovascular accidents in patients taking contraceptive pills: an analysis of 85 cases. J Neuroradiol 6:239-254, 1979 40. Irey NS, Manion WC, Taylor HB: Vascular lesions in women taking oral contraceptives. Arch Pathol 89:1-8, 1970 41. Manalo-Estrella P, Barker AE: Histopathologic findings in human aortic media associated with pregnancy: a study of 16 cases. Arch Pathol 83:336-341,1967 42. Ross R, Klebanoff SJ: The smooth muscle cell. I. In vivo synthesis of connective tissue proteins. J Cell Biol 50:159-171,1971 43. Kaufman J J , Maxwell MH: Upright aortography in the study of nephroptosis, stenotic lesions of the renal artery, and hypertension. Surgery 53:736-742, 1963 44. Leung DYM, Glagov S, Mathews MB: Cyclic stretching stimulates synthesis of matrix components by arterial smooth muscle cells in vitro. Science 191:475-477, 1976 45. Rothfield NJH: Fibromuscular arterial disease: experimental studies. Australas Radiol 14:294-297,1970 46. Ringel SP, Harrison SH, Norenberg MD, Austin JH: Fibromuscular dysplasia: multiple "spontaneous" dissecting aneurysms of the major cervical arteries. Ann Neurol 1:301-304, 1977 47. Young PH, Smith KR Jr, Crafts DC, Barner HB: Traumatic occlusion in fibromuscular dysplasia of the carotid artery. Surg Neurol 16:432-437, 1981 48. Halpern MM, Sanford HS, Viamonte M Jr: Renal-artery abnormalities in three hypertensive sisters: probable familial fibromuscular hyperplasia. JAMA 194:512-513, 1965 49. Plagnol P, Gillet JM, Cambuzat JM, Broussin J: Hypertension röno-vasculaire familiale. J Radiol Electrol Med Nucl 56:173-174, 1975 50. Rushton AR: The genetics of fibromuscular dysplasia. Arch Intern Med 140:233-236,1980 51. Keith TA III: Renovascular hypertension in black patients. Hypertension 4:438-443, 1982 52. Nakata Y: An experimental study on the vascular lesions caused by obstruction of the vasa vasorum. Jpn CircJ 31:275-287, 1967 53. Sottiurai V, Fry WJ, Stanley JC: Ultrastructural characteristics of experimental arterial medial fibroplasia induced by vasa vasorum occlusion. J Surg Res 24:169177, 1978 54. Wissler RW: The arterial medial cell, smooth muscle, or multifunctional mesenchyme? (editorial). Circulation 36:1-4, 1967 55. De Mendonca WC, Espat PA: Pheochromocytoma associated with arterial fibromuscular dysplasia. Am J Clin Pathol 75:749-754, 1981 56. Brewster DC, Jensen SR, Novelline RA: Reversible renal artery stenosis associated with pheochromocytoma. JAMA 248:1094-1096, 1982 57. Fievez M, Philippart F, Hustin J: Ergotism: anatomoclinical study of a case. Angiology 26:491-498, 1975 58. Regan JF, Poletti BJ: Vascular adventitial fibrosis in a patient taking methysergide maleate. JAMA 203:1069-1071, 1968 59. Pajewski M, Modai D, Wisgarten J, Freund E, Manor A, Starinski R: Iatrogenic arterial aneurysm associated with ergotamine therapy (letter to the editor). Lancet 2:934-935, 1981

FIBROMUSCULAR DYSPLASIA

949

60. Dornfeld L, Kaufman JJ: Immunologie considerations in renovascular hypertension. Urol Clin North Am 2:285-300, June 1975 61. Stewart DR, Price RA, Nebesar R, Schuster SR: Progressive peripheral fibromuscular hyperplasia in an infant: a possible manifestation of the rubella syndrome. Surgery 73:374-380, 1973 62. Lüscher T, Vetter H, Tenschert W, Greminger P, Pouliadis G, Kuhlmann U, Reutter F, Tuma J, Siegenthaler W, Vetter W: Problem cases in renovascular hypertension. Clin Nephrol 19:299-308,1983 63. Edwards BS, Stanson AW, Holley KE, Sheps SG: Isolated renal artery dissection: presentation, evaluation, management, and pathology. Mayo Clin Proc 57:564571, 1982 64. Ledingham JM: Experimental renal hypertension. Clin Nephrol 4:127-137, 1975 65. Hunt JC, Strong CG: Renovascular hypertension: mechanisms, natural history and treatment. Am J Cardiol 32:562-574, 1973 66. Pickering TG, Sos TA, Vaughan ED Jr, Case DB, Sealey JE, Harshfield GA, Laragh JH: Predictive value and changes of renin secretion in hypertensive patients with unilateral renovascular disease undergoing successful renal angioplasty. Am J Med 76:398-404, 1984 67. Lüscher TF, Greminger P, Kuhlmann U, Siegenthaler W, Largiader F, Vetter W: Renal venous renin determinations in renovascular hypertension: diagnostic and prognostic value in unilateral renal artery stenosis treated by surgery or percutaneous transluminal angioplasty. Nephron 44 (Suppl l):17-24, 1986 68. Juncos LI, Strong CG, Hunt JC: Prediction of results of surgery for renal and renovascular hypertension. Arch Intern Med 134:655-660, 1974 69. Marks LS, Maxwell MH, Varady PD, Lupu AN, Kaufman JJ: Renovascular hypertension: does the renal vein renin ratio predict operative results? J Urol 115:365-368, 1976 70. Tucker RM, Strong CG, Brennan LA Jr, Sheps SG, Brown RD, Weinshilboum RM: Renovascular hypertension: relationship of surgical curability to reninangiotensin activity. Mayo Clin Proc 53:373-377, 1978 •71. Strong CG, Hunt JC, Sheps SG, Tucker RM, Bernatz PE: Renal venous renin activity: enhancement of sensitivity of lateralization by sodium depletion. Am J Cardiol 27:602-611, 1971 72. Hasday JD, Sterns RH, Karch FE: Renal infarction due to renal artery dysplasia with dissection: report of a case in a normotensive patient. Am J Med 76:943-946, 1984 73. Elkik F, Corvol P, Idatte J-M, Menard J: Renal segmental infarction: a cause of reversible malignant hypertension. J Hypertens 2:149-156, 1984 74. Bron KM, Redman H: Renal arteriovenous fistula and fibromuscular hyperplasia: a new association. Ann Intern Med 68:1039-1043,1968 75. Oxman HA, Sheps SG, Bernatz PE, Harrison EG Jr: An unusual cause of renal arteriovenous fistula—fibromuscular dysplasia of the renal arteries: report of a case. Mayo Clin Proc 48:207-210, 1973 76. Grüntzig A, Kuhlmann U, Vetter W, Lütolf U, Meier B, Siegenthaler W: Treatment of renovascular hypertension with percutaneous transluminal dilatation of a renal-artery stenosis. Lancet 1:801-802, 1978 77. Kuhlmann U, Greminger P, Grüntzig A, Schneider E, Pouliadis G, Lüscher T, Steurer J, Siegenthaler W, Vetter W: Long-term experience in percutaneous transluminal dilatation of renal artery stenosis. Am J Med 79:692-698, 1985

950

FIBROMUSCULAR DYSPLASIA

78. Zech P, Finaz de Villaine J, Pozet N, Sassard J, Vincent M, Labeeuw M, Collard M, Hadj-Aissa A: Surgical versus medical treatment in renovascular hypertension: retrospective study of 166 cases. Nephron 44 (Suppl 1):105-108, 1986 79. Havelka J, Vetter H, Studer A, Greminger P, Liischer T, Wollnik S, Siegenthaler W, Vetter W: Acute and chronic effects of the angiotensin-converting enzyme inhibitor captopril in severe hypertension. Am J Cardiol 49:1467-1474, 1982 80. Franklin SS, Smith RD: A comparison of enalapril plus hydrochlorothiazide with standard triple therapy in renovascular hypertension. Nephron 44 (Suppl l):73-82, 1986 81. Foster JH, Dean RH, Pinkerton JA, Rhamy RK: Ten years experience with the surgical management of renovascular hypertension. Ann Surg 177:755-764, 1973 82. Foster JH, Maxwell MH, Franklin SS, Bleifer KH, Trippel OH, Julian OC, DeCamp PT, Varady PT: Renovascular occlusive disease: results of operative treatment. JAMA 231:1043-1048, 1975 83. Buda JA, Baer L, Parra-Carrillo JZ, Kashef MM, McAllister FF, Voorhees AB Jr, Pirani CL: Predictability of surgical response in renovascular hypertension. Arch Surg 111:1243-1247, 1976 84. Novick AC, Straffon RA, Stewart BH, Benjamin S: Surgical treatment of renovascular hypertension in the pediatric patient. J Urol 119:794-799,1978 85. Bergentz S-E, Ericsson BF, Husberg B: Technique and complications in the surgical treatment of renovascular hypertension. Acta Chir Scand 145:143-148, 1979 86. Lankford NS, Donohue JP, Grim CE, Weinberger MH: Results of surgical treatment of renovascular hypertension. J Urol 122:439-441, 1979 87. Whelton PK, Harris AP, Russell RP, Walsh PC, Williams GM, Harrington DP, Walker WG: Renovascular hypertension: comparison of medical and surgical therapy. Clin Sei 57 (Suppl 5):445S-447S, 1979 88. Lawrie GM, Morris GC Jr, Soussou ID, Starr DS, Silvers A, Glaeser DH, DeBakey ME: Late results of reconstructive surgery for renovascular disease. Ann Surg 191:528-533, 1980 89. Zuber J, Liischer T, Vetter W: Renovaskuläre Hypertonie in der Schweiz 1976-1978: eine Multizenterstudie. Schweiz Med Wochenschr 110:1096-1106, 1980 90. Stoney RJ, De Luccia N, Ehrenfeld WK, Wylie EJ: Aortorenal arterial autografts: long-term assessment. Arch Surg 116:1416-1421, 1981 91. Stanley JC, Whitehouse WM, Graham LM, Cronenwett JL, Zelenock GB, Lindenauer SM: Operative therapy of renovascular hypertension. Br J Surg 69 (Suppl):S63S66, 1982 92. Grim CE, Yune HY, Donohue JP, Weinberger MH, Dilley R, Klatte EC: Renal vascular hypertension: surgery vs. dilation. Nephron 44 (Suppl 1):96-100, 1986 93. Franklin SS, Young JD Jr, Maxwell MH, Foster JH, Palmer JM, Cerny J, Varady PD: Operative morbidity and mortality in renovascular disease. JAMA 231:11481153, 1975 94. Novick AC, Straffon RA, Stewart BH, Gifford RW, Vidt D: Diminished operative morbidity and mortality in renal revascularization. JAMA 246:749-753,1981 95. Novick AC, Straffon RA, Stewart BH: Surgical management of branch renal artery disease: in situ versus extracorporeal methods of repair. J Urol 123:311-316, 1980 96. Sos TA, Saddekni S, Pickering TG, Laragh JH: Technical aspects of percutaneous transluminal angioplasty in renovascular disease. Nephron 44 (Suppl l):45-50, 1986

Mayo Clin Proc, October 1987, Vol 62

97. Schwarten DE, Yune HY, Klatte EC, Grim CE, Weinberger MH: Clinical experience with percutaneous transluminal angioplasty (PTA) of stenotic renal arteries. Radiology 135:601-604, 1980 98. Colapinto RF, Stronell RD, Harries-Jones EP, Gildiner M, Hobbs BB, Farrow GA, Wilson DR, Morrow JD, Logan AG, Birch SJ: Percutaneous transluminal dilatation of the renal artery: follow-up studies on renovascular hypertension. AJR 139:727-732, 1982 99. Mahler F, Probst P, Haertel M, Weidmann P, Krneta A: Lasting improvement of renovascular hypertension by transluminal dilatation of atherosclerotic and nonatherosclerotic renal artery stenoses: a follow-up study. Circulation 65:611-617, 1982 100. Geyskes GG, Puylaert CBAJ, Oei HY, Mees EJD: Follow up study of 70 patients with renal artery stenosis treated by percutaneous transluminal dilatation. Br Med J [Clin Res] 287:333-336, 1983 101. Tegtmeyer CJ, Kellum CD, Ayers C: Percutaneous transluminal angioplasty of the renal artery: results and long-term follow-up. Radiology 153:77-84, 1984 102. Martin LG, Price RB, Casarella WJ, Sones PJ, Wells JO Jr, Zellmer RA, Chuang VP, Silbiger ML Jr, Berkman WA: Percutaneous angioplasty in clinical management of renovascular hypertension: initial and longterm results. Radiologv 155:629-633,1985 103. Millan VG, McCauley J, Kopelman RI, Madias NE: Percutaneous transluminal renal angioplasty in nonatherosclerotic renovascular hypertension: long-term results. Hypertension 7:668-674, 1985 104. Miller GA, Ford KK, Braun SD, Newman GE, Moore AV Jr, Malone R, Dunnick NR: Percutaneous transluminal angioplasty vs. surgery for renovascular hypertension. AJR 144:447-450, 1985 105. Martin LG, Casarella WJ, Alspaugh JP, Chuang VP: Renal artery angioplasty: increased technical success and decreased complications in the second 100 patients. Radiology 159:631-634, 1986 106. Beinart C, Sos TA, Saddekni S, Weiner MA, Sniderman KW: Arterial spasm during renal angioplasty. Radiology 149:97-100,1983 107. Puijlaert CBAJ, Mali WPTM, Rosenbusch G, van Straalen AM, Klinge J, Feldberg MAM: Delayed rupture of renal artery after renal percutaneous transluminal angioplasty. Radiology 159:635-637, 1986 108. Case DB, Atlas SA, Marion RM, Laragh JH: Long-term efficacy of captopril in renovascular and essential hypertension. Am J Cardiol 49:1440-1446, 1982 109. Hricik DE, Browning PJ, Kopelman R, Goorno WE, Madias NE, Dzau VJ: Captopril-induced functional renal insufficiency in patients with bilateral renalartery stenoses or renal-artery stenosis in a solitary kidney. N Engl J Med 308:373-376,1983 110. Lüscher TF, Vetter H, Siegenthaler W, Vetter W: Compliance in hypertension: facts and concepts. J Hypertens 3 (Suppl l):3-9, 1985 111. Mettinger KL: Fibromuscular dysplasia and the brain. II. Current concept of the disease. Stroke 13:53-58, 1982 112. So EL, Toole JF, Moody DM, Challa VR: Cerebral embolism from septal fibromuscular dysplasia of the common carotid artery. Ann Neurol 6:75-78, 1979 113. Wells RP, Smith RR: Fibromuscular dysplasia of the internal carotid artery: a long term follow-up. Neurosurgery 10:39-43, 1982 114. Havelius U, Hindfelt B, Brismar J, CronqvistS: Carotid fibromuscular dysplasia and paresis of lower cranial nerves (Collet-Sicard syndrome): case report. J Neurosurg 56:850-853, 1982

Mayo Clin Proc, October 1987, Vol 62

115. Andersen CA, Collins GJ Jr, Rich NM, McDonald PT: Spontaneous dissection of the internal carotid artery associated with fibromuscular dysplasia. Am Surg 46:263-266, 1980 116. McNeill DH Jr, Dreisbach J, Marsden RJ: Spontaneous dissection of the internal carotid artery: its conservative management with heparin sodium. Arch Neurol 37:54-55, 1980 117. Grotta JC, Ward RE, Flynn TC, Cullen ML: Spontaneous internal carotid artery dissection associated with fibromuscular dysplasia. J Cardiovasc Surg (Torino) 23:512-514,1982 118. Sato S, Hata J: Fibromuscular dysplasia: its occurrence with a dissecting aneurysm of the internal carotid artery. Arch Pathol Lab Med 106:332-335, 1982 119. Garcia-Merino JA, Gutierrez JA, Lopez-Lozano JJ, Marquez M, Lopez F, Liano H: Double lumen dissecting aneurysms of the internal carotid artery in fibromuscular dysplasia: case report. Stroke 14:815-818, 1983 120. Kalyan-Raman UP, Kowalski RV, Lee RH, Fierer JA: Dissecting aneurysm of superior cerebellar artery: its association with fibromuscular dysplasia. Arch Neurol 40:120-122, 1983 121. Bellot J, Gherardi R, Poirier J, Lacour P, Debrun G, Barbizet J: Fibromuscular dysplasia of cervicocephalic arteries with multiple dissections and a carotidcavernous fistula: a pathological study. Stroke 16:255261, 1985 122. Mas J-L, Goeau C, Bousser M-G, Chiras J, Verret J-M, Touboul P-J: Spontaneous dissecting aneurysms of the internal carotid and vertebral arteries—two case reports. Stroke 16:125-129, 1985 123. Chiras J, Marciano S, Vega Molina J, Touboul J, Poirier B, Bories J: Spontaneous dissecting aneurysm of the extracranial vertebral artery (20 cases). Neuroradiology 27:327-333,1985 124. Hieshima GB, Cahan LD, Mehringer CM, Bentson JR: Spontaneous arteriovenous fistulas of cerebral vessels in association with fibromuscular dysplasia. Neurosurgery 18:454-458, 1986 125. Palubinskas AJ, Newton TH: Fibromuscular hyperplasia of the internal carotid arteries. Radiol Clin Biol 34:365-370, 1965 126. Kalyanaraman UP, Elwood PW: Fibromuscular dysplasia of intracranial arteries causing multiple intracranial aneurysms. Hum Pathol 11:481-484, 1980 127. Handa J, Kamijyo Y, Handa H: Intracranial aneurysm associated with fibro-muscular hyperplasia of renal and internal carotid arteries. Br J Radiol 43:483-485, 1970 128. Bolander H, Hassler O, Liliequist B, West KA: Cerebral aneurysm in an infant with fibromuscular hyperplasia of the renal arteries: case report. J Neurosurg 49:756759,1978 129. Sahs AL, Perret G, Locksley HB, Nishioka H, Skultety FM: Preliminary remarks on subarachnoid hemorrhage. J Neurosurg 24:782-788,1966 130. Effeney DJ, Ehrenfeld WK, Stoney RJ, Wylie EJ: Fibromuscular dysplasia of the internal carotid artery. World J Surg 3:179-186, 1979 131. Ehrenfeld WK, Stoney RJ, Wylie EJ: Fibromuscular hyperplasia of the internal carotid artery. Arch Surg 95:284-287, 1967 132. Morris GC Jr, Lechter A, DeBakey ME: Surgical treatment of fibromuscular disease of the carotid arteries. Arch Surg 96:636-643,1968 133. Stanley JC, Fry WJ, Seeger JF, Hoffman GL, Gabrielsen TO: Extracranial internal carotid and vertebral artery fibrodysplasia. Arch Surg 109:215-222, 1974

FIBROMUSCULAR DYSPLASIA

951

134. Effeney DJ, Ehrenfeld WK, Stoney RJ, Wylie EJ: Why operate on carotid fibromuscular dysplasia? Arch Surg 115:1261-1263, 1980 135. Collins GJ Jr, Rich NM, Clagett GP, Spebar MJ, Salander JM: Fibromuscular dysplasia of the internal carotid arteries: clinical experience and follow-up. Ann Surg 194:89-96, 1981 136. Starr DS, Lawrie GM, Morris GC Jr: Fibromuscular disease of carotid arteries: long term results of graduated internal dilatation. Stroke 12:196-199, 1981 137. Danza R, Baldizän J, Navarro T: Surgery of carotid kinking and fibromuscular dysplasia. J Cardiovasc Surg (Torino) 24:628-633,1983 138. Levien LJ, Fritz VU, Lurie D, Cooke PA, Hertzanu Y: Fibromuscular dysplasia of the extracranial carotid arteries: case reports. S Afr Med J 65:261-265, 1984 139. Sundt TM Jr, Whisnant JP, Fode NC, Piepgras DG, Houser OW: Results, complications, and follow-up of 415 bypass operations for occlusive disease of the carotid system. Mayo Clin Proc 60:230-240,1985 140. Garrido E, Montoya J: Transluminal dilatation of internal carotid artery in fibromuscular dysplasia: a preliminary report. Surg Neurol 16:469-471,1981 141. Hasso AN, Bird CR, Zinke DE, Thompson JR: Fibromuscular dysplasia of the internal carotid artery: percutaneous transluminal angioplasty. AJR 136:955-960, 1981 142. Belän A, Veselä M, Vangk I, Weiss K, Peregrin JH: Percutaneous transluminal angioplasty of fibromuscular dysplasia of the internal carotid artery. Cardiovasc Intervent Radiol 5:79-81, 1982 143. Dublin AB, Baitaxe HA, Cobb CA III: Percutaneous transluminal carotid angioplasty in fibromuscular dysplasia: case report. J Neurosurg 59:162-165,1983 144. Tsai FY, Matovich V, Hieshima G, Shah DC, Mehringer CM, Tiu G, Higashida R, Pribram HFW: Percutaneous transluminal angioplasty of the carotid artery. AJNR 7:349-358,1986 145. Jooma R, Bradshaw JR, Griffith HB: Intimal dissection following percutaneous transluminal carotid angioplasty for fibromuscular dysplasia. Neuroradiology 27:181-182, 1985 146. Wesen CA, Elliott BM: Fibromuscular dysplasia of the carotid arteries. Am J Surg 151:448-451, 1986 147. Ripley HR, Levin SM: Abdominal angina associated with fibromuscular hyperplasia of the celiac and superior mesenteric arteries. Angiology 17:297-310,1966 148. Quirke P, Campbell I, Talbot IC: Ischaemic proctitis and adventitial fibromuscular dysplasia of the superior rectal artery. Br J Surg 71:33-38, 1984 149. Furrer J, Griintzig A, Kugelmeier J, Goebel N: Treatment of abdominal angina with percutaneous dilatation of an arteria mesenterica superior stenosis. Cardiovasc Intervent Radiol 3:43-44, 1980 150. Castaneda-Zuniga WR, Gomes A, Weens C, Ketchum D, Amplatz K: Transluminal angioplasty in the management of mesenteric angina. ROFO 137:330-332, 1982 151. Drury JK, Pollock JG: Subclavian arteriopathy in the young patient. Br J Surg 68:617-620, 1981 152. McCready RA, Pairolero PC, Hollier LH, Brown OW, Lie JT: Fibromuscular dysplasia of the right subclavian artery. Arch Surg 117:1243-1245, 1982 153. Iwai T, Konno S, Hiejima K, Satake S, Suzuki S, Hiranuma S, Kamiyama R: Fibromuscular dysplasia in the extremities. J Cardiovasc Surg (Torino) 26:496501, 1985 154. Motarjeme A, Keifer JW, Zuska AJ, Nabawi P: Percutaneous transluminal angioplasty for treatment of subclavian steal. Radiology 155:611-613, 1985

952

FIBROMUSCULAR DYSPLASIA

155. Twigg HL, Palmisano PJ: Fibromuscular hyperplasia of the iliac artery: a case report. Am J Roentgenol 95:418-423,1965 156. Najafi H: Fibromuscular hyperplasia of the external iliac arteries: an unusual cause of intermittent claudication. Arch Surg 92:394-396,1966 157. Home TW: Fibromuscular hyperplasia of the iliac arteries. Aust NZ J Surg 45:415-417, 1975 158. Thiele B, Geddes N, Johnson N, Macleish D, Royle J, Buxton B: Ruptured iliac aneurysms. Aust NZ J Surg 45:417-421, 1975 159. Mehigan JT, Stoney RJ: Arterial microemboli and fibromuscular dysplasia of the external iliac arteries. Surgery 81:484-486, 1977 160. Daskalakis MK: Fibromuscular hyperplasia of external iliac arteries. West J Med 128:345-347,1978 161. Houston C, Rosenthal D, Lamis PA, Stanton PE Jr: Fibromuscular dysplasia of the external iliac arteries: surgical treatment by graduated internal dilatation technique. Surgery 85:713-715,1979 162. Drury JK, Pollock JG: Fibromuscular dysplasia of the iliac arteries. Vase Surg 16:133-136,1982 163. Burri B, Fontolliet C, Ruegsegger C-H, Mosimann R: External iliac artery dissection due to fibromuscular dysplasia. Vasa 12:76-78, 1983 164. Katzen BT: Percutaneous transluminal angioplasty for arterial disease of the lower extremities. AJR 142:2325, 1984

Mayo Clin Proc, October 1987, Vol 62

165. James TN, Marshall TK: De subitaneis mortibus. XVII. Multifocal stenoses due to fibromuscular dysplasia of the sinus node artery. Circulation 53:736-742, 1976 166. Tongio J, Kieny R, Warter P: Coarctation de l'aorte abdominale et dysplasie des arteres ronales: a propos de quatre cas. Ann Radiol (Paris) 20:287-290, 1977 167. David M, Putelat R, Louis P, Weiller M, Briet S, Viard H: Coarctation de l'aorte abdominale associee ä une dysplasie des deux arteres rinales traitee par pontage puis par autotransplantation r£nale bilaterale. Ann ChirThorac Cardiovasc 17:197-202, 1978 168. Bopp P, Perrenoud J-J, Favre L, Faidutti B: Association of coarctation of the thoracic aorta with fibromuscular dysplasia of the renal arteries: a case report. Angiology 33:119-124, 1982 169. Malloy DS, Sangalang VE, Fräser GM: Cerebral infarction secondary to unsuspected intracranial fibromuscular dysplasia following bypass of aortic coarctation. Stroke 15:908-911,1984 170. Ecoiffier J, Fournier A, Leduc G, Plainfosse M-C: Quelle signification peut-on accorder a la decouverte arteriographique de "stenoses" au cours des pheochromocytomes. Presse Med 78:2325-2328,1970 171. Qunibi WJ, Taylor TK, Knight TF, Senekjian HO, Gomez L, Weinman EJ: Pheochromocytoma and fibromuscular hyperplasia. South Med J 72:1481-1482, 1979 172. Hudgins LB, Limbacher J P II: Fibromuscular dysplasia in Alport's syndrome. J Tenn Med Assoc 75:733735,1982