Fibromuscular Dysplasia 

Updated: Jul 27, 2018
Author: James A Wilson, MD, MSc, FRCPC; Chief Editor: Helmi L Lutsep, MD 

Overview

Practice Essentials

Fibromuscular dysplasia (FMD) is an angiopathy that affects medium-sized arteries predominantly in young women of childbearing age. Among patients with identified FMD, renal involvement occurs in 60-75%, cerebrovascular involvement in 25-30%, visceral involvement in 9%, and arteries of the limbs in about 5%.[1, 2] FMD occurs in most other medium-to-large arteries as well, including the coronary arteries,[3] the pulmonary arteries,[4] and the aorta.[5] See the image below.

Angiogram of the descending aorta demonstrates the Angiogram of the descending aorta demonstrates the stenoses of FMD in the renal arteries bilaterally.

Signs and symptoms

Most patients with craniocervical FMD are asymptomatic. No particular symptoms are pathognomonic for FMD. Any history compatible with a stroke in younger individuals may indicate underlying FMD. The family history should include information about relatives who have had vascular events at a young age.

In symptomatic patients, manifestations of FMD may include the following:

  • Nonspecific problems, such as headache, light-headedness, vertigo, and tinnitus

  • Neck pain or carotidynia

  • History of transient or permanent neurologic deficits of the face or extremities (eg, weakness or numbness)

  • Visual changes or speech difficulties

  • Symptoms compatible with a sentinel bleed (eg, a sudden explosive headache followed later by neck stiffness): May indicate an aneurysm that may be associated with FMD

  • Symptoms suggestive of noncraniocervical FMD, such as hypertension (renal involvement), abdominal pains or a history of ischemic bowel (mesenteric or visceral artery involvement), or intermittent leg claudication (extremity artery involvement)

Physical examination should include the following:

  • Thorough neurologic examination

  • Neurovascular examination, including auscultation for carotid and vertebral artery bruits

  • General physical examination that includes a search for signs of renal, visceral, and extremity artery involvement

See Clinical Presentation for more detail.

Diagnosis

Routine laboratory investigations are usually nonproductive but may show renal impairment.

Imaging considerations include the following:

  • A history of stroke or transient ischemic attack (TIA) in a young individual or a subarachnoid hemorrhage in a person of any age should prompt cerebrovascular imaging; such imaging is also indicated for any individual known to have FMD

  • Conventional angiography is standard for detecting FMD and its associated vascular lesions

  • Conventional cerebrovascular ultrasonography is unlikely to depict the carotid lesions of FMD

  • The sensitivity and specificity of computed tomography (angiography (CTA), time-of-flight (TOF) magnetic resonance angiography (MRA), or contrast-enhanced MRA (CE MRA) in this setting remain to be established

  • Conventional CT and MRI may be useful in finding ischemic strokes caused by arterial dissection or the FMD lesions themselves, as well as for detecting subarachnoid hemorrhage

Pathologically, FMD is classified into 3 main types, as follows[10, 11, 12] :

  • Intimal fibroplasia (< 10% of all cases of renal FMD)

  • Medial fibroplasia: Further classified into 3 subtypes: medial dysplasia (80% of renal cases and most carotid cases), perimedial fibroplasia (10-15% of all renal cases), and medial hyperplasia (1-2% of all renal cases)

  • Adventitial fibroplasia (< 1% of all renal cases)

Because these frequency figures are largely based on findings from renal studies, they may not reflect the distribution of FMD types in carotid disease.

See Workup for more detail.

Management

Partly because of the unknown etiology of FMD, no curative therapy exists. Fortunately, FMD is often benign when asymptomatic, and medical treatment is not indicated. In symptomatic cases, management depends on the presentation, as follows:

  • Presentation with hypertension: The patient should be evaluated by a nephrologist and possibly considered for vascular intervention

  • Presentation as a TIA or ischemic stroke: If the patient presents within 3 hours of onset, consider intravenous tissue plasminogen activator (tPA); intra-arterial mechanical embolectomy and intra-arterial pharmacologic fibrinolysis may be considered to extend the acute treatment window to 6 hours; if tPA treatment is employed, avoid anticoagulants and antiplatelet agents for at least 24 hours

  • The diagnosis of FMD should be considered in any young individual presenting with a stroke or subarachnoid hemorrhage. Fortunately, cerebral angiography is the investigation of choice to detect not only FMD but also arterial dissection, vasculitis, and aneurysms, which are other major etiologies of stroke in this population. Thus, cerebral angiography should be performed if another cause for the stroke is not clear. The treatment options are influenced by the findings on angiography

  • Presentation with only FMD identified on angiography: Administer antiplatelet agents

  • Presentation with arterial dissection and FMD identified on cerebral angiography: Initially, focus on the dissection; consider anticoagulation after cerebral hemorrhage has been ruled out

  • Presentation with subarachnoid hemorrhage: Focus acute treatment on preventing rebleeding, arterial vasospasm, and further ischemic cerebral injury; close aneurysms; subsequently, manage conservatively unless further history is consistent with thromboembolic phenomena

Considerations for surgical treatment include the following:

  • Surgical vascular reconstruction of renal FMD has met with good success,[13] but the role of surgery in carotid and vertebrobasilar FMD is not well understood

  • With respect to stroke prophylaxis, the lesions in FMD are not amenable to endarterectomy; thus, surgical management is used as a last resort

  • A few cases with vascular graft placements and surgical bypass of FMD lesions have been reported

  • Aneurysms that may coexist with FMD should be managed in a similar manner to those that are not associated with FMD

  • Interventional radiologic management of FMD lesions may be suitable for some patients, especially those who are not good surgical candidates

See Treatment and Medication for more detail.

Background

Fibromuscular dysplasia (FMD) was first observed in 1938 by Leadbetter and Burkland in a 5-year-old boy, and described as a disease of the renal arteries. Involvement of the craniocervical arteries was recognized in 1946 by Palubinskas and Ripley.

FMD is an angiopathy that affects medium-sized arteries predominantly in young women of childbearing age. FMD most commonly affects the renal arteries and can cause refractory renovascular hypertension. Of patients with identified FMD, renal involvement occurs in 60-75%, cerebrovascular involvement occurs in 25-30%, visceral involvement occurs in 9%, and arteries of the limbs are affected in about 5%.[1, 2] Case reports have shown FMD in most other medium-to-large arteries as well, including the coronary arteries[3] , the pulmonary arteries[4] , and the aorta[5] . In 26% of patients, disease is found in more than one arterial region[6] .

In patients with identified cephalic FMD, 95% have internal carotid artery involvement and 12-43% have vertebral artery involvement. Although FMD can affect arteries of any size[7] , involvement of smaller ones, including intracranial vessels, is rare. Although an early autopsy series of 819 consecutive patients found the prevalence of FMD in the internal carotid arteries to be 1%[8] , a larger, more recent autopsy series of 20,244 patients recently identified the overall prevalence of FMD of the internal carotid arteries to be only 0.02%[9] . From a neurologic perspective, FMD is an important cause of stroke in young adults.

Pathophysiology

The etiology of FMD is not known, although the histopathologic findings have been described in detail (see Histologic Findings).

Although the etiology of FMD is unknown, several other associated vascular pathologies have been identified. In 1982, Mettinger and Ericson[14] scrutinized 4000 consecutively performed cerebral angiographies and found 37 that were consistent with FMD. Of these, 19 patients had aneurysms. In 1988, Cloft et al performed a meta-analysis including 498 FMD patients as well as examined 117 of their own patients and found a combined prevalence of aneurysms to be 7.3%.[15]

In 1975, Stanley et al found that 8 of their 17 cerebrovascular FMD cases had intracranial aneurysms, and they proposed a classification system that includes a "medial fibroplasias with aneurysms" subtype.[11] The beadlike dilatations observed within FMD lesions share gross and histologic characteristics of aneurysms. The casual link between FMD and aneurysms is less clear but is possibly related to an underlying connective tissue problem that results in loss of arterial wall strength. This wall weakness may allow for vessel dilation (aneurysm formation and beading in FMD) as well as injury, which then causes compensatory fibroplasia. Besides aneurysms, many case series and reports have identified FMD in patients presenting with arterial dissection.[16, 17]

FMD is a predisposing factor in 15% of spontaneous cervical carotid dissections. Dissections in FMD are more commonly multiple than in patients without an identified underlying arteriopathy.

FMD lesions likely predispose the artery to dissection through weakening of the arterial wall. Although the multiple manifestations of a structural arteriopathy in FMD hint of a genetic cause, such as collagen or elastin mutation, epidemiologic data suggesting familial transmission are generally weak.

The increased incidence of FMD in women as compared with men suggests a possible hormonal or genetic influence. Some authors have proposed the sex difference to be related to immune system functioning, but overt inflammation, as is observed in most classic autoimmune diseases, is histologically lacking.

Many reports exist of familial occurrences of FMD, mostly in siblings. Some studies have even suggested that familial occurrence is relatively common. For example, Rushton in 1980 suggested familial occurrences in relatives of 12 out of 20 identified probands.[18] However, histologic proof was established in only the index cases, and vascular events such as early strokes and hypertension were used to identify the other affected family members. Most large series have reported that the great preponderance of FMD cases are sporadic. Bilateral renal FMD has been noted in a pair of identical twins.[19]

In case reports, FMD has been associated with mutations in collagen[20] , with cutis laxa[21] , and with alpha1-antitrypsin deficiency[22] . Associative links to neurofibromatosis, Alport syndrome, and pheochromocytoma have also been suggested.[2]

Epidemiology

Frequency

United States

Although early autopsy and radiologic series suggested that FMD involving the craniocervical arteries occurs at a frequency of approximately 1%, a more recent large series looking at FMD in the carotid arteries only suggests a lower frequency, on the order of 0.02%.[9]

International

The frequency is unknown.

Mortality/Morbidity

FMD generally follows a benign course and is frequently an incidental finding. However, cranial involvement bears worse prognosis because of the occurrence of dissection and strokes and the coexistence of saccular aneurysms. Specific mortality and morbidity data are lacking.

Regarding the risk of recurrent carotid artery dissection, de Bray et al prospectively reviewed 103 consecutive patients with carotid artery dissection with follow-up for an average of 4 years. Of those, 5 had recurrent dissections and 4 of the 5 patients with recurrent dissections were diagnosed with FMD. If considering the presentation of recurrent dissection of the carotid artery, FMD was associated in 80% of their series.[23]

Race

Whites are considered to be more commonly affected than blacks, although specific statistics on racial predilection are not available.

Sex

FMD occurs more frequently in women, at a ratio of approximately 3:1 to 4:1.

Age

FMD most commonly presents in young to middle-aged adults. One angiographic series found a mean age of 48 years with a range of 24-70 years.[14] Cases have even been described in the pediatric population, including infantile-onset cases.[24]

 

Presentation

History

Most patients with craniocervical FMD are asymptomatic. Others report nonspecific problems such as headache, lightheadedness, vertigo, and tinnitus. Neck pain or carotidynia may be an initial presenting symptom due to arterial dissection. The symptoms of stroke can be varied but most often involve the anterior circulation because of the predilection of FMD to affect the extracranial carotid arteries.

Patients may provide a history of transient or permanent neurologic deficits of the face or extremities such as weakness or numbness, or they may experience visual changes or speech difficulties. No particular symptoms are pathognomonic for FMD, and any history compatible with a stroke in younger individuals may indicate underlying FMD. The family history should include information about relatives who have had vascular events at a young age.

One report notes an extremely unfortunate case of locked-in syndrome due to autopsy-proven basilar artery FMD.[16] FMD may be complicated by stroke because of direct effects of craniocervical stenosis, dissection, or intracranial aneurysm, or the indirect effects of concomitant renovascular hypertension.

Symptoms compatible with a sentinel bleed, namely a sudden explosive headache followed later by neck stiffness, may signify the existence of an aneurysm, which in turn, may be associated with FMD.

A review of symptoms may provide clues of noncraniocervical FMD. Long-standing involvement of the renal arteries may lead to a history of hypertension. Rarely, abdominal pains, and even a history of ischemic bowel, may indicate mesenteric or visceral artery involvement. Vascular compromise of the limbs by FMD lesions may cause ischemic symptoms such as intermittent leg claudication. A case of FMD associated with spinal subdural hematoma has been reported.[25]

Physical

Because of the broad possibilities of neurologic dysfunction due to stroke caused by FMD, a thorough neurologic examination should be performed. Findings may include anything from cranial nerve deficits to weakness, numbness, and coordination difficulties.

Sensitive signs of motor dysfunction such as pronator drift and plantar responses may yield deficits when formal power assessment does not. The neurovascular examination would not be complete without auscultation for carotid and vertebral artery bruits. If a headache history is provided, assessment for meningismus (eg, nuchal rigidity, Kernig sign, Brudzinski sign) may prove positive.

Because of the systemic nature of FMD, the general physical examination should include a search for signs of renal, visceral, and limb arterial involvement. These signs may include hypertension, decreased peripheral pulses, and even asymmetric limb pressures. Bruits may be found on auscultation of the renal, abdominal, iliac, or subclavian arteries.

Causes

The cause of FMD is unknown, despite some speculations related to its associations with some rare genetic conditions and predilection for young white females. Strokes can be caused by the FMD stenoses themselves, generally by thromboembolic events. Even without trauma, FMD lesions predispose the afflicted individual to arterial dissection, which in turn can cause embolic events or, rarely, local thrombosis and massive hemispheric stroke. Hypertension due to renovascular FMD may be a risk factor for lacunar and large vessel infarcts and even intracerebral hemorrhage.

 

DDx

Diagnostic Considerations

Other problems to be considered include the following:

  • Arterial dissection

  • Stroke

  • Atherosclerosis

  • Vasculitis

  • Vasospasm secondary to subarachnoid hemorrhage

  • Vasospasm secondary to angiographic contrast agent and/or catheter

  • Vasospasm secondary to stimulant use

  • Degos disease (malignant atrophic papulosis)

  • Varicella zoster virus (VZV) vasculitis

  • Other infectious vasculitis

Differential Diagnoses

 

Workup

Laboratory Studies

Although usually nonproductive, routine laboratory investigations may show renal impairment (eg, with high creatinine or BUN levels).

Imaging Studies

For a more focused analysis of imaging studies in FMD, please see Fibromuscular Dysplasia (Carotid Artery).

The history of stroke or transient ischemic attack in a young individual or a subarachnoid hemorrhage in a person of any age should prompt imaging of the cerebrovascular system. Further, any individual known to have FMD (eg, renal disease detected) should undergo cerebrovascular imaging to assess for craniocervical involvement and aneurysms.

Conventional angiography remains the criterion standard to detect FMD and its associated vascular lesions (eg, aneurysms, dissections). (See images below.)

FMD lesions typically show a beading pattern. With the most common subtype of FMD, medial fibroplasias, the dilated arterial segments are often larger in diameter than the original vessel. This is not the case with perimedial fibroplasias, in which the beads are up to, but not greater than, the caliber of the original vessel. On the other hand, the intimal fibroplasia and the medial hyperplasia subtypes tend to show long tubular stenoses.[26]

In the internal carotid arteries, these lesions are usually extracranial at the C1-2 level. Stenoses associated with arterial bifurcations, such as at the bifurcation of the common carotid, are more frequently atherosclerotic in nature. Four-vessel angiography should be performed because of the high incidence of multiple vessel involvement.

In 1986, Luscher et al identified 24 patients with cerebrovascular FMD and found that 17% had involvement of the vertebral arteries, 17% had brachiocephalic or subclavian involvement, and 4% had basilar artery disease.[6]

Digital subtraction angiogram of the right interna Digital subtraction angiogram of the right internal carotid artery demonstrates an irregular extracranial portion that is consistent with FMD.
Conventional angiogram of the left carotid artery Conventional angiogram of the left carotid artery demonstrates a 1.5-cm, long, smooth, severe stenosis of the extracranial internal carotid artery. Note that the artery is not completely occluded and a thin continuous string of contrast is present along the length of the stenosis. This smooth tubular stenosis is suggestive of the intimal fibroplasia form of FMD but can be observed with any of the subtypes.
Cerebral angiogram of the left carotid artery terr Cerebral angiogram of the left carotid artery territory demonstrates a long, irregular stenosis with a string-of-beads appearance along the entire extracranial length of the internal carotid artery (ICA). This is consistent with the most common medial dysplasia form of fibromuscular dysplasia. Also note similar involvement of the first 3 cm of the external carotid artery (ECA). Such extensive ICA involvement, as well as ECA involvement, is atypical. Note sparing of the carotid bulb.
Lateral view of a right carotid angiogram demonstr Lateral view of a right carotid angiogram demonstrates multiple stenoses of FMD of the internal carotid artery. The string of beads appearance is suggestive of the medial dysplasia form of FMD.
Anteroposterior view of a right carotid angiogram Anteroposterior view of a right carotid angiogram demonstrates FMD of the extracranial portion of the right internal carotid artery.
Angiogram of the descending aorta demonstrates the Angiogram of the descending aorta demonstrates the stenoses of FMD in the renal arteries bilaterally.
Angiogram of the right vertebral artery demonstrat Angiogram of the right vertebral artery demonstrating irregular stenoses of fibromuscular dysplasia at the level of C2-3.

Conventional cerebrovascular ultrasonography is unlikely to depict the carotid lesions of FMD because they are typically sufficiently distal to the carotid bifurcation so as to avoid detection by standard carotid duplex investigation.

Submandibular insonation with a transcranial Doppler probe directed at the high cervical segments can be used to investigate the distal cervical artery and has moderate sensitivity for detecting FMD.

Doppler scanning of the vertebrobasilar system may reveal reversal of flow (including subclavian steal), but it is not in any way sensitive or specific for FMD.

To the authors' knowledge, no large studies have been conducted to assess the sensitivity or specificity of CT angiography (CTA), time-of-flight (TOF) magnetic resonance angiography (MRA), or contrast-enhanced MRA (CE MRA) in the diagnosis of craniocervical FMD. However, these modalities, especially CTA and CE MRA, can show surprising vascular detail and may be sufficiently sensitive for the confident detection of FMD. Due to the risk of conventional angiography, there is certainly a need to identify comparably sensitive noninvasive imaging techniques. Fortunately, we have some clues from the renal literature that the above noninvasive techniques could be comparable.

CTA is continuously improving in resolution and may be used to detect the stenosis associated with FMD, but only recent-generation CTA equipment reliably shows sufficient detail to identify the classic string of beads pattern of most FMD cases. de Monye advocates the use of CTA as a noninvasive modality to diagnose FMD, albeit with only a series of 2 patients.[27] Regarding FMD of the renal arteries, the sensitivity of CTA has been compared directly with conventional angiography.[28] In their series of 21 patients with 40 total lesions identified on conventional angiography, all lesions were identified using several modalities of CTA (multiplanar reformatted images, maximum intensity projections, and shaded-surface display). Suspecting that CTA of the carotid arteries shares similar sensitivity to conventional angiography in identifying craniocervical FMD would be reasonable.

Findings on TOF MRA often suggest vessel stenoses, but this study has insufficient resolution to demonstrate a string-of-beads pattern suggestive of FMD.

Contrast-enhanced MRA will likely perform better than TOF MRA, but this has not yet been studied in detail regarding craniocervical FMD. However, similar to CTA, the renal literature has looked at FMD of the renal arteries using CE MRA. In a series of 25 patients, Willoteaux found the sensitivity and specificity of CE MRA in renal FMD to be 97% and 93% respectively.[29] They found 68% sensitivity in diagnosing stenosis, 95% in identifying the string of pearls, and 100% sensitivity in identifying an aneurysm. Thus, although CE MRA in craniocervical FMD has not specifically been assessed, it is likely that this modality is reasonably sensitive as compared with the more invasive criterion standard.

Conventional CT scanning and MRI may be useful in finding ischemic strokes caused by arterial dissection or the FMD lesions themselves. These modalities can also be useful in detecting subarachnoid hemorrhage.

CTA and MRA can often detect aneurysms greater than about 0.3 cm.

Histologic Findings

Pathologically, FMD is a nonatherosclerotic noninflammatory narrowing of medium-sized arteries characterized by fibrodysplastic changes. In 1979, Bragin and Cherkasov described the ultrastructural changes that occur in FMD as smooth muscle assuming fibroblastic characteristics.[30] FMD has been classified according to the arterial wall layer that is predominantly affected.[10]

The pathologic classification of FMD is as follows:[10, 11, 12]

Intimal fibroplasia

See the list below:

  • This accounts for fewer than 10% of all cases of renal FMD.

  • Collagen deposition occurs in the intima of the vessels.

  • Internal elastic lamina may be disrupted.

  • The lumen may be concentrically narrowed in a relatively short region, causing a ringlike stenosis on angiography, or it may be narrowed over a longer region as a smooth tubular stenosis.

Medial fibroplasia (3 subtypes)

Medial dysplasia

  • This accounts for 80% of renal cases and most carotid cases.

  • Regions of thick, fibrodysplastic, collagenized tunica media alternate with regions of thinned media.

  • The result is the classic string-of-beads appearance on angiography.

Perimedial fibroplasia

  • This accounts for 10-15% of all renal cases of FMD.

  • Patchy collagen deposition is observed in the outer media without disruption of the external elastic lamina.

  • This subtype can also result in the string-of-beads appearance on angiography, but the beads are not dilated to a larger diameter than that of the original vessel.

Medial hyperplasia

  • This accounts for 1-2% of all renal cases of FMD.

  • True smooth muscle concentric hyperplasia without fibrotic changes is noted.

  • The result is a smooth stenosis on radiographic study.

Adventitial fibroplasia

See the list below:

  • This form results in fewer than 1% of all renal cases of FMD.

  • Dense collagen replaces the normally loose connective tissue of the adventitia.

The percentage occurrence of each type of FMD is largely based on findings from large renal studies and may not reflect the distribution of FMD types in carotid disease. In fact, the medial dysplasia type may be even more predominant when carotid FMD is considered alone.

Staging

No formal staging system exists for FMD, although 4-vessel angiography of the cerebrovasculature is used to identify the extent of the craniocervical disease and the presence of comorbid dissections and aneurysms.

 

Treatment

Medical Care

Partly because of the unknown etiology of FMD, no curative therapy exists. Fortunately, FMD is often benign when asymptomatic, and medical treatment is not indicated. Patients presenting with hypertension should be evaluated by a nephrologist and possibly considered for vascular intervention.

When FMD manifests as a transient ischemic attack or as an ischemic stroke, then initial management depends on many factors. If the patient presents in the emergency department with symptoms of stroke within 4.5 hours of onset, then they may be considered for intravenous (IV) tissue plasminogen activator (tPA) treatment (see Acute Stroke Management). Intra-arterial mechanical embolectomy may be considered to extend the acute treatment window to 24 hours. If TPA treatment is employed, then anticoagulants and antiplatelet agents are generally avoided for at least the ensuing 24 hours.

The diagnosis of FMD should be considered in any young individual presenting with a stroke or subarachnoid hemorrhage. Fortunately, cerebral angiography is the investigation of choice to detect not only FMD but also arterial dissection, vasculitis, and aneurysms, which are other major etiologies of stroke in this population. Thus, cerebral angiography should be performed if another cause for the stroke is not clear. The treatment options are influenced by the findings on angiography.

If only FMD is identified on angiography, medical treatment usually incorporates antiplatelet agents, similar to the treatment of atherosclerotic disease. Often, daily aspirin is considered first-line therapy, and another antiplatelet agent is substituted or added if another ischemic event occurs (such as clopidogrel or combination acetylsalicylic acid and extended-release dipyridamole).

If arterial dissection with FMD is identified with cerebral angiography, then initial treatment primarily addresses the dissection (see Dissection Syndromes). Although evidence from randomized trials is lacking, anticoagulation is often used after cerebral hemorrhage has been ruled out. Anticoagulation is with heparin initially, then Coumadin is administered on an outpatient basis for 3-6 months. Some neurologists advocate reassessment of the arteries for dissection before discontinuation of anticoagulation and initiation of an antiplatelet agent for life. Often, if the dissection could be observed with MRA or CTA, these modalities are used in follow-up because of its less invasive nature.

If the presentation is that of subarachnoid hemorrhage, then acute treatment is primarily focused on preventing rebleeding, and preventing arterial vasospasm and further ischemic cerebral injury. Aneurysms may be closed by endovascular coiling or surgical clipping. Nimodipine, a calcium channel blocker, is generally used to reduce vasospasm-mediated brain injury. See Cerebral Aneurysms for a more in-depth discussion of aneurysm management.

After the aneurysms have been dealt with, either surgically or through an endovascular approach, then unless further history is consistent with thromboembolic phenomena, management may be conservative. Antiplatelets are unnecessary if the FMD lesions themselves are asymptomatic and not causing emboli.

Some authors have suggested that FMD could be caused by arterial wall injury fragility followed by hemodynamic stress. Hence, treating FMD by reducing hemodynamic stress (ie, aggressive blood pressure control) may be reasonable.[31]

Surgical Care

Surgical vascular reconstruction of renal FMD has met with good success.[13] However, because the end organ of cervicocranial FMD is the brain, more serious risks are involved. Thus, the role of surgery in carotid and vertebrobasilar FMD is not well understood.

Although medical management of stroke prophylaxis in FMD is quite similar to the management of atherosclerotic disease, the lesions in FMD are not amenable to endarterectomy. Thus, surgical management is used as a last resort in cases where stenosis is critical and global cerebral hypoperfusion is an issue or for ischemic events refractory to medical management. No trials exist comparing medical and surgical management of cerebrovascular FMD. However, many authors have published series of operative graduated dilatation of FMD stenosis and report good results.[32, 33, 34] (See images below.)

Illustration of the operative approach of graduate Illustration of the operative approach of graduated dilatation of the internal carotid artery (ICA). The common carotid and external carotid arteries are cross-clamped, and the superior thyroid artery is clipped while the ICA is isolated, opened, and dilated with progressively larger dilators. This technique has been shown to be successful in the management of medically refractive FMD stenoses.
Illustration depicts the intraluminal appearance o Illustration depicts the intraluminal appearance of graduated dilatation of the stenoses of FMD. The dilator is passed into the vessel and opens the bandlike narrowings.

A few cases with vascular graft placements and surgical bypass of FMD lesions have been reported.

Aneurysms that may coexist with FMD should be managed in a similar manner to non-FMD–associated ones.

Because of the emergence of endoluminal angioplasty and stenting for cerebrovascular disease, interventional radiologic management of FMD lesions may be suitable for some patients, especially those who are not good surgical candidates. Again, no studies have assessed this management option as compared to more established medical or surgical treatment, but it may be deemed an appropriate option in some instances. One case report describes a good outcome after 9 months of follow-up in a patient with bilateral carotid stents placed for bilateral medically-refractory symptomatic lesions.[35]

Consultations

A stroke presentation, whether acute or not, is usually managed by a neurologist. If associated aneurysms or subarachnoid hemorrhages are detected, then a neurosurgeon and interventional radiologist should be consulted. If a history of chest pain is noted, this may signify FMD in the coronary arteries, and a cardiologist should be consulted. If blood pressure is elevated, then the renovasculature should be assessed and a nephrologist consulted if necessary. Symptoms of an ischemic gut should be managed by a general surgeon, and limb claudication should be assessed by a vascular surgeon.

Diet

No specific dietary modifications are indicated in FMD. If a stroke has occurred, then a swallowing assessment may be required and the diet modified accordingly.

Activity

Activity restrictions should be individualized depending on the clinical details and possible neurologic deficits. Neck trauma, including chiropractic manipulation, should be avoided if craniocervical FMD is established because of the possibility of dissection. If cerebral aneurysms exist, strenuous activity that would increase blood pressure should be avoided.

 

Medication

Medication Summary

As discussed above, acute treatment of any ischemic stroke may involve tPA, regardless of the presence or absence of FMD.

Secondary prevention of stroke generally involves the use of antiplatelet agents, and failure of a first agent results in either the switch to another agent or the addition of a second antiplatelet agent. Selection of a particular antiplatelet agent is variable, depending on physician preference. The complication of arterial dissection is generally treated with anticoagulation, first intravenously then orally. Finally, subarachnoid hemorrhage due to aneurysm rupture precludes anticoagulation and indicates a need for antivasospastic medications.

Fibrinolytic agents

Class Summary

tPA exerts an effect on fibrinolytic system to convert plasminogen to plasmin. They are used for dissolving blood clots and have a role in the acute management of ischemic strokes.

Alteplase (Activase)

Used in management of acute ischemic stroke, acute MI, and PE. Safety and efficacy with concomitant heparin or aspirin during first 24 h after symptom onset not investigated.

Antiplatelet agents

Class Summary

These agents are used for secondary stroke prophylaxis after previous stroke or transient ischemic attack.

Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)

Treats mild to moderate pain and headache. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2. Generally considered first-line therapy in the secondary prophylaxis of cerebrovascular disease.

Clopidogrel (Plavix)

Selectively inhibits ADP binding to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, inhibiting platelet aggregation.

May have positive influence on several hemorrhagic parameters and may exert protection against atherosclerosis (inhibition of platelet function and changes in hemorrhagic profile).

Ticlopidine (Ticlid)

Second-line antiplatelet therapy for patients who cannot tolerate acetylsalicylic acid therapy or for whom such therapy is unsuccessful. Rarely used because of serious adverse effects and replacement by newer agents.

Aspirin 25 mg/Dipyridamole 200 mg (Aggrenox)

Drug combination with antithrombotic action. Aspirin inhibits prostaglandin synthesis, preventing formation of platelet-aggregating thromboxane A2. May be used in low dose to inhibit platelet aggregation and improve complications of venous stasis and thrombosis. Dipyridamole is a platelet adhesion inhibitor that possibly inhibits RBC uptake of adenosine, itself an inhibitor of platelet reactivity. May also inhibit phosphodiesterase activity, leading to increased cyclic-3', 5'-adenosine monophosphate levels in platelets and formation of the potent platelet activator thromboxane A2.

Anticoagulants

Class Summary

The use of anticoagulation in the acute management of stroke has been under hot debate for many years. However, many neurologists advocate the use of heparin acutely in stroke in the setting of an arterial dissection. Heparin is used acutely in this case, followed by several months of warfarin.

Heparin

Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

Most centers have protocols to titrate heparin rate to achieve specific anticoagulation levels on blood work.

Warfarin (Coumadin)

Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders.

Calcium channel blockers

Class Summary

These agents are used in cases of subarachnoid hemorrhage.

Nimodipine (Nimotop)

To improve neurologic impairments resulting from vasospasm after subarachnoid hemorrhage caused by a ruptured congenital intracranial aneurysm in patients who are in good neurologic condition postictus.

Studies show benefit on the severity of neurologic deficits caused by cerebral vasospasm after subarachnoid hemorrhage, but no evidence indicates that the drug either prevents or relieves spasm of the cerebral arteries. Actual mechanism of action unknown, and a neuroprotective effect is suggested.

Therapy should start within 96 h of the subarachnoid hemorrhage. If capsule cannot be swallowed because patient is undergoing surgery or unconscious, a hole can be made at both ends of the capsule with an 18-gauge needle and the contents extracted into a syringe and emptied into the patient's in situ nasogastric tube and flush with 30-mL isotonic saline.

 

Follow-up

Further Outpatient Care

Neurorehabilitation generally helps to recover function if any residual neurologic deficits are present.

Further Inpatient Care

Physical and occupational therapy and speech therapy may be important aspects of patient care should neurologic deficits exist.

Inpatient & Outpatient Medications

See the list below:

  • As mentioned above, life-long antiplatelet agents are generally suggested if a stroke occurred because of their benefit in reducing stroke and their relatively low morbidity.

  • Given the potential pro-coagulant effects of estrogen, especially in smokers, oral contraceptives and hormonal replacement therapy is often avoided. No data exists to support or refute this strategy.

Deterrence/Prevention

See the list below:

  • Lifestyle changes that minimize the risk of vascular disease should be stressed.

  • These changes include quitting smoking, weight control, doing exercise, and eating a healthy diet.

Complications

See the list below:

  • The complications of FMD can be diverse, notably because it is a systemic vascular disease. Fortunately, most patients have relatively isolated disease, and invasive measures during follow-up are not required.

  • Blood pressure should be monitored carefully throughout the patient's lifetime because of the possibility of renovascular hypertension.

  • Any symptoms compatible with ischemia and angiographic findings should prompt consideration of FMD as the underlying etiology. Symptoms include neurologic deficits, angina pectoris, limb claudication, and abdominal pain.

Prognosis

See the list below:

  • Statistics on the natural course of cerebrovascular FMD are not available, especially because most cases are symptomatic and relatively benign.

  • Case series tend to present a relatively favorable picture of long-term stroke-free survival, both in medically and in surgically managed patients. For example, in a 1981 report, Collins et al monitored 18 patients after surgical dilatation for a mean of just over 4 years, and none had strokes.[34] They monitored 5 patients with global symptoms (eg, hypoperfusion and not embolic events) and conservative therapy for a mean of 42 months, and none had strokes.

  • Saccular aneurysm rupture has such a high mortality that autopsy series may be biased in their detection of FMD. The presence of saccular aneurysms likely poses the greatest morbidity and mortality threat, especially if blood pressure is not controlled.

  • In a prospective series of patients with carotid artery dissection observed for an average of 4 years, of those with recurrence (5 of 103), 80% had FMD.[23]

Patient Education

See the list below:

  • Patients with FMD who have experienced strokes should receive proper education in this regard. Further education regarding FMD should help patients recognize further symptoms that may indicate disease progression or complications.

  • Education regarding other risk factors for stroke should be provided where applicable. Topics should include abstinence from smoking, the benefits of a healthy diet, and good glycemic control.

  • Patients should be informed about the risk of dissection and cautioned to avoid neck trauma and rigorous neck manipulations.

  • For patient education resources, see the Brain and Nervous System, as well as Aneurysm, Brain and Stroke.

 

Questions & Answers

Overview

What is fibromuscular dysplasia (FMD)?

What are the signs and symptoms of fibromuscular dysplasia (FMD)?

What should be included in the physical exam for fibromuscular dysplasia (FMD)?

What is included in the workup of fibromuscular dysplasia (FMD)?

What are the types of fibromuscular dysplasia (FMD)?

How is fibromuscular dysplasia (FMD) treated?

What is the role of surgery in the treatment of fibromuscular dysplasia (FMD)?

What is fibromuscular dysplasia (FMD)?

What is the pathophysiology of fibromuscular dysplasia (FMD)?

What is the role of genetics in the pathophysiology of fibromuscular dysplasia (FMD)?

What is the prevalence of fibromuscular dysplasia (FMD) in the US?

What is the global prevalence of fibromuscular dysplasia (FMD)?

What is the morbidity associated with fibromuscular dysplasia (FMD)?

What are the racial predilections of fibromuscular dysplasia (FMD)?

What are the sexual predilections of fibromuscular dysplasia (FMD)?

Which age groups have the highest prevalence of fibromuscular dysplasia (FMD)?

Presentation

Which clinical history findings are characteristics of fibromuscular dysplasia (FMD)?

Which physical findings are characteristic of fibromuscular dysplasia (FMD)?

What causes fibromuscular dysplasia (FMD)?

DDX

Which conditions should be included in the differential diagnoses of fibromuscular dysplasia (FMD)?

What are the differential diagnoses for Fibromuscular Dysplasia?

Workup

What is the role of lab testing in the diagnosis of fibromuscular dysplasia (FMD)?

What is the role of angiography in the evaluation of fibromuscular dysplasia (FMD)?

What is the role of CT and MRI in the diagnosis of fibromuscular dysplasia (FMD)?

What is the role of ultrasonography in the diagnosis of fibromuscular dysplasia (FMD)?

Which histologic findings are characteristic of fibromuscular dysplasia (FMD)?

Which histologic findings are characteristic of intimal fibroplasia type of fibromuscular dysplasia (FMD)?

Which histologic findings are characteristic of the adventitial fibroplasia type of fibromuscular dysplasia (FMD)?

Which histologic findings are characteristic of the medial dysplasia subtype of fibromuscular dysplasia (FMD)?

Which histologic findings are characteristic of the perimedial fibroplasia subtype of fibromuscular dysplasia (FMD)?

Which histologic findings are characteristic of the medial hyperplasia subtype of fibromuscular dysplasia (FMD)?

How is fibromuscular dysplasia (FMD) staged?

Treatment

How is fibromuscular dysplasia (FMD) treated?

What is the role of surgery in the treatment of fibromuscular dysplasia (FMD)?

Which specialist consultations are beneficial to patients with fibromuscular dysplasia (FMD)?

Which dietary modifications are used in the treatment of fibromuscular dysplasia (FMD)?

Which activity modifications are used in the treatment of fibromuscular dysplasia (FMD)?

Medications

What is the role of medications in the treatment of fibromuscular dysplasia (FMD)?

Which medications in the drug class Calcium channel blockers are used in the treatment of Fibromuscular Dysplasia?

Which medications in the drug class Anticoagulants are used in the treatment of Fibromuscular Dysplasia?

Which medications in the drug class Antiplatelet agents are used in the treatment of Fibromuscular Dysplasia?

Which medications in the drug class Fibrinolytic agents are used in the treatment of Fibromuscular Dysplasia?

Follow-up

What is the role of neurorehabilitation in the treatment of fibromuscular dysplasia (FMD)?

What is the role of physical therapy in the treatment of fibromuscular dysplasia (FMD)?

Which medications are used in the treatment of fibromuscular dysplasia (FMD)?

Which lifestyle changes are beneficial to patients with fibromuscular dysplasia (FMD)?

What are the possible complications of fibromuscular dysplasia (FMD)?

What is the prognosis of fibromuscular dysplasia (FMD)?

What is included in patient education about fibromuscular dysplasia (FMD)?