Fibromuscular Dysplasia Workup

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

• 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.^[23]
  • 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 internal carotid artery demonstrates an irregular extracranial portion that is consistent with FMD. 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 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 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 demonstrates FMD of the extracranial portion of the right internal carotid artery. Angiogram of the descending aorta demonstrates the stenoses of FMD in the renal arteries bilaterally. 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.^[24] Regarding FMD of the renal arteries, the sensitivity of CTA has been compared directly with conventional angiography.^[25] 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.^[26] 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.

No other tests are specifically indicated in the workup of FMD.

In general, procedures are not indicated in the diagnosis of FMD.

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.^[27] FMD has been classified according to the arterial wall layer that is predominantly affected.^[28]

The pathologic classification of FMD is as follows:^{[28, 12, 29]}

• Intimal fibroplasia

  • 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

  • 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.

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.