Fibromuscular Dysplasia 

  • Author: James A Wilson, MD, MSc, FRCPC; Chief Editor: Helmi L Lutsep, MD   more...
 
Updated: Jan 13, 2010
 

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.

Next

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[10] 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%.[11]

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.[12] 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.[13, 14]

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.[15] 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.[16]

In case reports, FMD has been associated with mutations in collagen[17] , with cutis laxa[18] , and with alpha1-antitrypsin deficiency[19] . Associative links to neurofibromatosis, Alport syndrome, and pheochromocytoma have also been suggested.[2]

Previous
Next

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.[20]

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.[10] Cases have even been described in the pediatric population, including infantile-onset cases.[21]

Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

James A Wilson, MD, MSc, FRCPC  Neurologist and Clinical Neurophysiologist, Oconee Neurology Services

James A Wilson, MD, MSc, FRCPC, is a member of the following medical societies: American Academy of Neurology and Ontario Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Richard L Hughes, MD  Associate Professor, Department of Neurology, University of Colorado School of Medicine; Director, University of Colorado Affiliated Hospitals Stroke Project; Chief, Division of Neurology, Denver Health Medical Center

Richard L Hughes, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Medical Association, and North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Jeffrey L Saver, MD  Director, Stroke Center, Professor, Department of Neurology, University of California at Los Angeles Medical Center

Jeffrey L Saver, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Neurological Association, and National Stroke Association

Disclosure: Boehringer-Ingelheim - Secondary Prevention Consulting fee Consulting; Talacris Consulting fee Consulting; ImaRx Consulting fee Consulting

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Howard S Kirshner, MD  Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center

Howard S Kirshner, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neurorehabilitation, National Stroke Association, Phi Beta Kappa, and Tennessee Medical Association

Disclosure: Boehringer Ingelheim Honoraria Speaking and teaching; BMS/Sanofi Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD  Professor, Department of Neurology, Oregon Health & Science University; Associate Director, Oregon Stroke Center

Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology and American Stroke Association

Disclosure: Co-Axia Consulting fee Review panel membership; Talecris Consulting fee Review panel membership; AGA Medical Consulting fee Review panel membership; Boehringer Ingelheim Honoraria Speaking and teaching; Concentric Medical Consulting fee Review panel membership; Abbott Consulting fee Consulting; Sanofi Consulting

References

  1. Luscher TF, Lie JT, Stanson AW, et al. Arterial fibromuscular dysplasia. Mayo Clin Proc. Oct 1987;62(10):931-52. [Medline].

  2. Gray GH, Young JR, Olin JW. Miscellaneous arterial diseases. In: Young JR, Olin JW, Bartholomew J, eds. Peripheral Vascular Diseases. 2nd ed. St Louis: Mosby-Yearbook; 1996:425-40.

  3. James TN. Morphologic characteristics and functional significance of focal fibromuscular dysplasia of small coronary arteries. Am J Cardiol. Apr 3 1990;65(14):12G-22G. [Medline].

  4. Campman SC, Holmes JF, Sokolove PE, et al. Pulmonary arterial fibromuscular dysplasia: a rare cause of fulminant lunghemorrhage. Am J Forensic Med Pathol. Mar 2000;21(1):69-73. [Medline].

  5. Maresi E, Becchina G, Ottoveggio G, et al. Arrhythmic sudden cardiac death in a 3-year-old child with intimal fibroplasia of coronary arteries, aorta, and its branches. Cardiovasc Pathol. Jan-Feb 2001;10(1):43-8. [Medline].

  6. Luscher TF, Keller HM, Imhof HG, et al. Fibromuscular hyperplasia: extension of the disease and therapeutic outcome. Results of the University Hospital Zurich Cooperative Study on Fibromuscular Hyperplasia. Nephron. 1986;44 Suppl 1:109-14. [Medline].

  7. Hill LD, Antonius JI. Arterial dysplasia: an important surgical lesion. Arch Surg. Apr 1965;90:585-95. [Medline].

  8. Heffelfinger MJ, Holley KE, Havrison EG. Arterial fibromuscular dysplasia studied at autopsy [abstract]. Am J Clin Pathol. 1970;54:274.

  9. Schievink WI, Bjornsson J. Fibromuscular dysplasia of the internal carotid artery: a clinicopathological study. Clin Neuropathol. Jan-Feb 1996;15(1):2-6. [Medline].

  10. Mettinger KL, Ericson K. Fibromuscular dysplasia and the brain. I. Observations on angiographic, clinical and genetic characteristics. Stroke. Jan-Feb 1982;13(1):46-52. [Medline].

  11. Cloft HJ, Kallmes DF, Kallmes MH, et al. Prevalence of cerebral aneurysms in patients with fibromuscular dysplasia:a reassessment. J Neurosurg. Mar 1998;88(3):436-40. [Medline].

  12. Stanley JC, Gewertz BL, Bove EL, et al. Arterial fibrodysplasia. Histopathologic character and current etiologic concepts. Arch Surg. May 1975;110(5):561-6. [Medline].

  13. Arunodaya GR, Vani S, Shankar SK, et al. Fibromuscular dysplasia with dissection of basilar artery presenting as "locked-in-syndrome". Neurology. Jun 1997;48(6):1605-8. [Medline].

  14. Eachempati SR, Sebastian MW, Reed RL 2nd. Posttraumatic bilateral carotid artery and right vertebral artery dissections in a patient with fibromuscular dysplasia: case report and review of the literature. J Trauma. Feb 1998;44(2):406-9. [Medline].

  15. Rushton AR. The genetics of fibromuscular dysplasia. Arch Intern Med. Feb 1980;140(2):233-6. [Medline].

  16. Bigazzi R, Bianchi S, Quilici N, et al. Bilateral fibromuscular dysplasia in identical twins. Am J Kidney Dis. Dec 1998;32(6):E4. [Medline].

  17. Tromp G, Wu Y, Prockop DJ, et al. Sequencing of cDNA from 50 unrelated patients reveals that mutations inthe triple-helical domain of type III procollagen are an infrequent causeof aortic aneurysms. J Clin Invest. Jun 1993;91(6):2539-45. [Medline].

  18. McKusick VA. Heritable Disorders of Connective Tissue. 4th ed. St Louis: Mosby-Yearbook; 1972:382-6.

  19. Schievink WI, Meyer FB, Parisi JE, Wijdicks EF. Fibromuscular dysplasia of the internal carotid artery associated with alpha1-antitrypsin deficiency. Neurosurgery. Aug 1998;43(2):229-33; discussion 233-4. [Medline].

  20. de Bray JM, Marc G, Pautot V, Vielle B, Pasco A, Lhoste P. Fibromuscular dysplasia may herald symptomatic recurrence of cervical artery dissection. Cerebrovasc Dis. 2007;23(5-6):448-52. [Medline].

  21. Lee EK, Hecht ST, Lie JT. Multiple intracranial and systemic aneurysms associated withinfantile-onset arterial fibromuscular dysplasia. Neurology. Mar 1998;50(3):828-9. [Medline].

  22. Kim SD, Park JO, Kim SH, Lee YH, Lim DJ, Park JY. Spontaneous thoracic spinal subdural hematoma associated with fibromuscular dysplasia. J Neurosurg Spine. May 2008;8(5):478-81. [Medline].

  23. Mettinger KL. Fibromuscular dysplasia and the brain. II. Current concept of the disease. Stroke. Jan-Feb 1982;13(1):53-8. [Medline].

  24. de Monyé C, Dippel DW, Dijkshoorn ML, Tanghe HL, van der Lugt A. MDCT detection of fibromuscular dysplasia of the internal carotid artery. AJR Am J Roentgenol. April 2007;188(4):W367-9. [Medline].

  25. Sabharwal R, Vladica P, Coleman P. Multidetector spiral CT renal angiography in the diagnosis of renal artery fibromuscular dysplasia. Eur J Radiol. March 2007;61(3):520-7. [Medline].

  26. Willoteaux S, Faivre-Pierret M, Moranne O, Lions C, Bruzzi J, Finot M, et al. Fibromuscular dysplasia of the main renal arteries: comparison of contrast-enhanced MR angiography with digital subtraction angiography. Radiology. December 2006;241(3):922-9. [Medline].

  27. Bragin MA, Cherkasov AP. [Morphogenesis of fibromuscular dysplasia of the renal arteries (anultrastructural study)]. Arkh Patol. 1979;41(2):46-52. [Medline].

  28. Harrison EG Jr, McCormack LJ. Pathologic classification of renal arterial disease in renovascular hypertension. Mayo Clin Proc. Mar 1971;46(3):161-7. [Medline].

  29. Begelman SM, Olin JW. Fibromuscular dysplasia. Curr Opin Rheumatol. Jan 2000;12(1):41-7. [Medline].

  30. Kimura H, Hosoda K, Hara Y, Kohmura E. A very unusual case of fibromuscular dysplasia with multiple aneurysms of the vertebral artery and posterior inferior cerebellar artery. J Neurosurg. Dec 2008;109(6):1108-12. [Medline].

  31. Reiher L, Pfeiffer T, Sandmann W. Long-term results after surgical reconstruction for renal artery fibromuscular dysplasia. Eur J Vasc Endovasc Surg. Dec 2000;20(6):556-9. [Medline].

  32. Van Damme H, Sakalihasan N, Limet R. Fibromuscular dysplasia of the internal carotid artery. Personal experience with 13 cases and literature review. Acta Chir Belg. Aug 1999;99(4):163-8. [Medline].

  33. Chiche L, Bahnini A, Koskas F, Kieffer E. Occlusive fibromuscular disease of arteries supplying the brain: results of surgical treatment. Ann Vasc Surg. Sep 1997;11(5):496-504. [Medline].

  34. Collins GJ Jr, Rich NM, Clagett GP, et al. Fibromuscular dysplasia of the internal carotid arteries. Clinical experience and follow-up. Ann Surg. Jul 1981;194(1):89-96. [Medline].

  35. Finsterer J, Strassegger J, Haymerle A, Hagmüller G. Bilateral stenting of symptomatic and asymptomatic internal carotid artery stenosis due to fibromuscular dysplasia. J Neurol Neurosurg Psychiatry. Nov 2000;69(5):683-6. [Medline].

  36. Leadbetter WF, Burkland CD. Hypertension in unilateral renal disease. J Urol. 1938;39:611-26.

  37. Leary MC, Finley A, Caplan LR. Cerebrovascular Complications of Fibromuscular Dysplasia. Curr Treat Options Cardiovasc Med. Jun 2004;6(3):237-248. [Medline].

  38. Olin JW. Recognizing and managing fibromuscular dysplasia. Cleve Clin J Med. Apr 2007;74(4):273-4, 277-82. [Medline].

  39. Palubinskas AJ, Ripley HR. Fibromuscular hyperplasia in extrarenal arteries. Radiology. 1946;82:451-55.

  40. Vuong PN, Desoutter P, Mickley V. Fibromuscular dysplasia of the renal artery responsible for renovascular hypertension: a histological presentation based on a series of 102 patients. Vasa. Feb 2004;33(1):13-8. [Medline].

 
Previous
Next
 
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.
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 of graduated dilatation of the stenoses of FMD. The dilator is passed into the vessel and opens the bandlike narrowings.
Illustration depicts the locations of FMD lesions, which differentiate regions with typical and atypical angiographic appearances of this disease.
Digital subtraction angiography of the left internal carotid artery distribution demonstrates a large 1.5-cm-diameter aneurysm of the right anterior communicating artery. Aneurysms may be associated with systemic vasculopathies such as FMD.
Small infarct in woman with fibromuscular dysplasia from dissected vertebral artery. An incidental aneurysm, or ovoid diverticula, is noted in the supraclinoid left internal carotid artery.
Small infarct in woman with fibromuscular dysplasia from dissected vertebral artery. An incidental aneurysm, or ovoid diverticula, is noted in the supraclinoid left internal carotid artery. Dissected vertebral artery.
Small infarct in woman with fibromuscular dysplasia from dissected vertebral artery. An incidental aneurysm, or ovoid diverticula, is noted in the supraclinoid left internal carotid artery. Internal carotid angiogram.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.