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October 1, 2018

Fibromuscular Dysplasia and Its Neurologic Manifestations: A Systematic Review

Author Affiliations
  • 1Normandie Université, Université Caen Normandie, Institut National de la Santé et de la Recherche Médicale U1237, Centre Hospitalier et Universitaire Caen, Caen, France
  • 2Department of Neurology, University of Virginia Health System, Charlottesville
  • 3Department of Public Health Sciences, University of Virginia Health System, Charlottesville
  • 4Department of Radiology, University of Lyon, Hôpitaux de Lyon, Lyon, France
  • 5Paris-Descartes University, Institut National de la Santé et de la Recherche Médicale UMR970, Assistance-Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, Paris, France
  • 6Department of Neurology, Memory Clinic, Bordeaux University Hospital, University of Bordeaux, Bordeaux, France
  • 7Institut National de la Santé et de la Recherche Médicale U1219, Bordeaux Population Health Research Center, Bordeaux, France
  • 8Heart & Vascular Institute, Cleveland Clinic, Cleveland, Ohio
  • 9Department of Neurology, Centre Hospitalier et Universitaire Fort-de-France, Martinique, French West Indies
  • 10Department of Paediatrics, University of Calgary, Calgary, Alberta, Canada
  • 11Service de Médecine Vasculaire, Université de Saint-Etienne, Centre Hospitalier et Universitaire Saint-Etienne, Saint-Etienne, France
  • 12Stroke Center, University of Utah, Salt Lake City
  • 13Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York
  • 14Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Brussels, Belgium
  • 15Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
  • 16Department of Medicine, University of Virginia Health System, Charlottesville
JAMA Neurol. 2019;76(2):217-226. doi:10.1001/jamaneurol.2018.2848
Key Points

Question  What are the neurologic manifestations of fibromuscular dysplasia?

Findings  This systematic review describes the epidemiologic characteristics, clinical and radiologic manifestations, prognosis, and management of fibromuscular dysplasia involving the cervical or intracranial arteries.

Meaning  Cerebrovascular fibromuscular dysplasia is now considered as frequent as renal fibromuscular dysplasia, and longitudinal, international cohort studies with outcomes and genetic sequencing are needed to further understand its clinical course and enable the development of evidence-based treatments.


Importance  Data on neurologic manifestations of fibromuscular dysplasia (FMD) are rare, and current knowledge remains limited.

Objectives  To present a comprehensive review of the epidemiologic characteristics, management, and prognosis of the neurologic manifestations associated with cerebrovascular FMD (ie, involving cervical or intracranial arteries) and to guide future research priorities.

Evidence Review  References were identified through searches of PubMed from inception to December 2017 using both the medical subject headings and text words. Additional sources were also identified by reviewing reference lists of relevant articles and through searches of the authors’ personal files. Selected articles described at least 1 clinical or radiologic feature and/or outcome of cerebrovascular FMD. Isolated case reports could be included if they described interesting or noteworthy manifestations of FMD.

Findings  A total of 84 relevant references were identified. Diagnosis of cerebrovascular FMD is based on the appearance of alternating arterial dilatation and constriction (“string of beads”) or of focal narrowing, with no sign of atherosclerotic or inflammatory lesions. Although the diagnosis is easily apparent on results of radiographic imaging, making a diagnosis can be challenging in children or individuals with atypical phenotypes, such as purely intracranial FMD and arterial diaphragm. Involvement of multiple arteries is common, and there is increased incidence of cervical artery dissection and intracranial aneurysms. A variant in the PHACTR1 gene has been associated with FMD as well as cervical artery dissection and migraine, although less than 5% of cases of FMD are familial. Headaches, mainly of the migraine type, are observed in up to 70% of patients with FMD. Cerebrovascular FMD is mostly asymptomatic, but the most frequent neurologic manifestations include transient ischemic attack and ischemic stroke, notably in the presence of associated cervical artery dissection. Other conditions associated with FMD include subarachnoid hemorrhage and, rarely, intracranial hemorrhage. Management relies on observational data and expert opinion. Antiplatelet therapy is considered reasonable to prevent thromboembolic complications. Endovascular therapy is typically restricted to cases with symptomatic stenosis despite optimal medical therapy or in those with rupture of an intracranial aneurysm.

Conclusions and Relevance  Longitudinal cohort studies of individuals of multiple ethnicities with biosampling are needed to better understand the risk factors, pathophysiological features, and outcomes of FMD. Patient advocacy groups could assist researchers in answering patient-centered questions regarding FMD.

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