Carotid arteryAuthor:

Dr. Enache Iulia-Ioana, MD

Twitter: @IuliaIEnache

Fibromuscular dysplasia (FMD) causes non-atherosclerotic, non-inflammatory architectural changes in the musculature of medium or small arteries, resulting primarily in stenosis. It is an idiopathic disease which usually involves multiple arteries, commonly the cervical arteries at their extracranial level, as well as the renal arteries, but many others may be affected as well.(1,2) Women comprise the vast majority of patients with FMD. Although less frequent, men can also develop FMD, and they may experience a more aggressive disease course characterized by a higher incidence of aneurysms and dissections.(3)

Establishing a diagnosis of FMD relies on either a focal or multifocal (“string of beads”) angiographic aspect. It should not be presumed that the patient has FMD simply based on the existence of a vessel wall anomaly, such as aneurysms, sinuosity or dissection; however, if a patient is found to fulfill criteria for a focal or multifocal variant of FMD, discovering such anomalies in a different vascular territory essentially means the patient has a multivessel involvement. (1)

Cervical artery dissection can occur in FMD patients, as mentioned, and it is actually considered a cardinal sign of cerebrovascular FMD.(1) According to the US registry of FMD, a quarter of these patients suffered from an episode of arterial dissection.(4) Whereas currently, specific genetic testing isn’t warranted for FMD, it seems a certain genetic constellation such as the PHACTR1 FMD rs9349379-A risk-allele may be associated with cervical artery dissection in particular; the same allele is a protective factor against atherosclerosis of the coronary arteries.(5) The treatment approach in cases of dissection associated with FMD remains the same, as supported by the CADISS trial and the guidelines.(6) Endovascular therapy perhaps would warrant additional caution, however an increased occurrence of vascular injury or pseudoaneurysms has not been observed as of yet.(1)

The main presentation of intracranial FMD is typically an unruptured aneurysm. Patients diagnosed with FMD in any location should undergo brain imaging with CTA or MRA to screen for intracranial aneurysms, as their prevalence is notably higher compared to the general population.(1,2) In a study with 1,112 female patients, 669 (60.2%) had received intracranial imaging at the time of enrollment. Among the 669 patients analyzed, 86 (12.9%; 95% CI, 10.3%-15.9%) were found to have at least one intracranial aneurysm. Among these 86 patients, 25 (53.8%) had multiple intracranial aneurysms.(7) Whether FMD increases the risk for aneurysmal rupture remains, however, to be seen.(8)

Of particular note is the connection between reversible cerebral vasoconstriction syndrome (RCVS) and FMD. On one hand, RCVS may be confused for FMD, as it has been shown that RCVS can actually not just impact cerebral arteries, but systemic arterial beds as well.(9,10) On the other hand, according to recent studies, a certain subtype of FMD (carotid web) may increase the risk of RCVS.(11) Besides, renal artery stenosis that is associated with FMD could lead to an excessive sympathetic activity, in turn causing RCVS; a synergic effect can be determined if a FMD-associated carotid artery dissection also occurs, with concurrent, unpredictable catecholamine feedback.(12)

All in all, FMD seems to be an appealing topic of discussion in cerebrovascular research, as there is a significant number of unknown variables in terms of genetics, prognosis, and the impact of treatment.

Acknowledgments

 I wish to show my mentor, dr. Manea Maria Mirabela, MD, PhD, FEBN, a small token of my gratitude. Thank you for inspiring me to become a better version of myself every day.


References:

  1. Gornik HL, Persu A, Adlam D, Aparicio LS, Azizi M, Boulanger M, et al. First International Consensus on the diagnosis and management of fibromuscular dysplasia. Vasc Med. 2019 Apr;24(2):164–89.
  2. Persu A, Giavarini A, Touzé E, Januszewicz A, Sapoval M, Azizi M, et al. European consensus on the diagnosis and management of fibromuscular dysplasia. J Hypertens. 2014 Jul;32(7):1367–78.
  3. Kim ESH, Olin JW, Froehlich JB, Gu X, Bacharach JM, Gray BH, et al. Clinical manifestations of fibromuscular dysplasia vary by patient sex: a report of the United States registry for fibromuscular dysplasia. J Am Coll Cardiol. 2013 Nov 19;62(21):2026–8.
  4. Kadian-Dodov D, Gornik HL, Gu X, Froehlich J, Bacharach JM, Chi YW, et al. Dissection and Aneurysm in Patients With Fibromuscular Dysplasia: Findings From the U.S. Registry for FMD. J Am Coll Cardiol. 2016 Jul 12;68(2):176–85.
  5. Gupta RM, Hadaya J, Trehan A, Zekavat SM, Roselli C, Klarin D, et al. A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of Endothelin-1 Gene Expression. Cell. 2017 Jul 27;170(3):522-533.e15.
  6. Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial. The Lancet Neurology. 2015 Apr;14(4):361–7.
  7. Lather HD, Gornik HL, Olin JW, Gu X, Heidt ST, Kim ESH, et al. Prevalence of Intracranial Aneurysm in Women With Fibromuscular Dysplasia. JAMA Neurol. 2017 Sep;74(9):1081–7.
  8. Etminan N, Rinkel GJ. Unruptured intracranial aneurysms: development, rupture and preventive management. Nat Rev Neurol. 2016 Dec;12(12):699–713.
  9. Mukerji SS, Buchbinder BR, Singhal AB. Reversible cerebral vasoconstriction syndrome with reversible renal artery stenosis. Neurology. 2015 Jul 14;85(2):201–2.
  10. John S, Hajj-Ali RA, Min D, Calabrese LH, Cerejo R, Uchino K. Reversible cerebral vasoconstriction syndrome: Is it more than just cerebral vasoconstriction? Cephalalgia. 2015 Jun 1;35(7):631–4.
  11. Santos Neto EPD, Sousa ÍA de, Ricarte IF, Pontes-Neto OM. Reversible Cerebral Vasoconstriction Syndrome And Fibromuscular Dysplasia: An Epiphenomenon Or A Causal Relationship? Acta Neurol Taiwan. 2024 Sep 30;33(3):122–6.
  12. Field D, Kleinig T, Thompson P, Kimber T. Reversible cerebral vasoconstriction, internal carotid artery dissection and renal artery stenosis. Cephalalgia. 2010 Aug 1;30(8):983–6.

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