Edit concept Question Editor Create issue ticket

Fibromuscular Dysplasia

FMD

Fibromuscular dysplasia (FMD) is a condition characterized by vascular stenosis, obstruction or aneurysm which are nonatherosclerotic and noninflammatory in origin.


Presentation

FMD is generally asymptomatic. Some of the nonspecific symptoms include headache, light headedness, vertigo and tinnitus. Arterial dissection may present itself as carotidynia or neck pain in initial stages. Stroke may be presented with varying symptoms but generally involve anterior circulation due to tendency of FMD to strike the extracranial carotid arteries.

Facial or extremity neurologic deficits manifested as weakness or numbness, speech impediment and visual changes are some of the symptoms associated with FMD. There is no pathognomonic symptom for FMD and any previous episode of stroke in younger patients indicate FMD. FMD is often found to have a strong inheritance pattern therefore any significant family history of vascular events at young age should always be studied.

Basilar artery FMD induced locked-in syndrome was reported in a young man at autopsy [12]. Cases of FMD are often complicated by direct effects of craniocervical dissection, stenosis, or aneurysm in case of stroke or by the indirect effects of simultaneous renovascular hypertension. FMD associated aneurysms is suspected in case of sudden explosive headache followed by neck stiffness due to sentinel bleed.

A close study of symptoms presented may help in accurate diagnosis of noncraniocervical FMD. For e.g. a history of hypertension suggest the role of renal artery FMD. Abdominal pains, a history of intestinal ischemia may point towards the presence of visceral or mesenteric artery involvement in rare cases. Intermittent leg pain due to limited blood supply indicate the presence of FMD lesions. Spinal subdural hematoma induced by FMD has also been reported [13].

Renal Artery Stenosis
  • Renal angioplasty is effective for long-term control of hypertension in patients with renal-artery stenosis due to fibromuscular dysplasia or unilateral non-ostial atheroma.[ncbi.nlm.nih.gov]
  • KEYWORDS: fibromuscular dysplasia; kidney transplantation; percutaneous transluminal angioplasty; renal artery stenosis[ncbi.nlm.nih.gov]
  • Diethylene triamine penta acetic acid renogram showed a small left kidney due to renal artery stenosis.[ncbi.nlm.nih.gov]
  • Renal angioplasty is effective for long-term control of hypertension in patients with renal-artery stenosis due to fibromuscular dysplasia or unilateral non-ostial atheroma. (N Engl J Med 1983; 309:274–9.)[doi.org]
  • Based on the procedural reports, these patients were separated into two cohorts: patients with isolated FMD (n 59) and patients with concomitant atherosclerotic renal artery stenosis and FMD (ARAS-FMD) (n 25).[ncbi.nlm.nih.gov]
Jaundice
  • Moreover, reticulocytosis, which is not corresponding to the degree of anemia, with jaundice and splenomegaly are major diagnostic criteria. Causative gene is located at SEC23B.[ncbi.nlm.nih.gov]
Hypertension
  • BACKGROUND: Renovascular hypertension accounts for 51-52% of all cases of hypertension in the general population, but plays a major role in treatable causes for hypertension in the young.[ncbi.nlm.nih.gov]
  • -P.B.), France; Hypertension Unit, CHU Timone, Marseille, France (F.S.); Department of Radiology, CHU Gabriel-Montpied, Clermont-Ferrand, France (L.B.); Hypertension Unit, CHU Rangueil, Toulouse, France (B.B.); Hypertension Unit, Hôpital Cardiologique[ncbi.nlm.nih.gov]
  • KEYWORDS: Fibromuscular dysplasia; Hypertension; Renal artery stenosis; Renovascular hypertension; Screening; Secondary hypertension[ncbi.nlm.nih.gov]
  • LESSONS: To our knowledge, this is the first bilateral common and internal iliac arterial FMD case in China, with unique asymptomatic dissection, aneurysm, and renovascular hypertension.[ncbi.nlm.nih.gov]
  • METHOD: In 58 hypertensive patients with multifocal renal artery FMD (off medication) and 116 matched controls with essential hypertension, we measured renal blood flow (Xenon washout method) per kidney and drew blood samples from the aorta and both renal[ncbi.nlm.nih.gov]
Pulse Deficit
  • Peripheral pulse deficits were uncommon and were documented at the doralis pedis and/or posterior tibial arteries in 5.0% and brachial and/or radial arteries in 0.9% of patients.[doi.org]
Left Ventricular Dysfunction
  • In this study, we report the case of a 1-day-old infant who presented with severe left ventricular dysfunction immediately after birth, and subsequently died 3 days postnatally.[ncbi.nlm.nih.gov]
Frozen Shoulder
  • She was treated for left frozen shoulder and supportive treatment for audible bruit for four years. She was referred from her general physician to a neurosurgeon because of left arm weakness.[ncbi.nlm.nih.gov]
Brachydactyly
  • Grange syndrome is an autosomal-recessive condition characterized by severe and early-onset vascular disease similar to FMD and variable penetrance of brachydactyly, syndactyly, bone fragility, and learning disabilities.[ncbi.nlm.nih.gov]
Bilateral Flank Pain
  • We report the case of a previously healthy 43-year-old white man presenting with acute bilateral flank pain. The pain was more severe on the left side.[ncbi.nlm.nih.gov]
  • This article reports the case of a previously healthy 37-year-old man presenting with acute-onset, severe, bilateral flank pain.[ncbi.nlm.nih.gov]
Headache
  • Headache is an extremely common and important symptom reported by patients with FMD, although the precise mechanism of headache in this population is not yet known.[ncbi.nlm.nih.gov]
  • Headaches were a common symptom (60.0% of patients), with classical migraine-type headaches reported in 32.2%. Severe headaches occurred weekly in 13.1% of patients and daily in 12.5% of patients.[doi.org]
  • All children presented with hypertension and many presented with headache and abdominal bruits.[ncbi.nlm.nih.gov]
  • Abstract A 26-year-old woman developed headache, diplopia, and pulsatile tinnitus in 10 days.[ncbi.nlm.nih.gov]
  • FMD in the carotid arteries may cause headaches or pulsatile tinnitus.[raredr.com]
Radiculomyelopathy
  • Disappearance of her audible bruit immediately after surgery and gradual improvement of her cervical radiculomyelopathy were observed after two years of clinical follow-up.[ncbi.nlm.nih.gov]

Workup

Diagnosis of FMD has two phases:

  1. Rule out the presence of atherosclerosis which share most of the symptoms of FMD through physical examination and by checking the cholesterol and sugar levels in blood.
  2. Diagnosis of fibromuscular dysplasia by:
  • Catheter-based angiography is a procedure in which a thin tube is inserted into one of the arteries to reach the suspected location. The site is examined with the aid of micro quantities of dye injected via catheter with subsequent visualization using X-rays
  • Doppler ultrasound is a noninvasive imaging technique using sound waves emitted by a transducer. It helps in establishing the FMD induced stenosis of arteries. The ultrasound helps in determining the speed of blood flow within the vessels. Slow movement indicates FMD
  • Computerized tomography (CT) angiogram helps in identifying narrowed or blocked arteries [13]. 
  • Magnetic resonance imaging (MRI) aids in imaging the soft tissues in the body and in case of FMD the collection of cells obstructing the artery confirms diagnosis [13].

Imaging test showing a "string of beads" is the hall mark image observed in usual FMD cases. Aggressive forms of FMD usually have a even appearance.

Treatment

Medical therapy and surveillance are the treatments options available for managing patients with symptomatic FMD. Endovascular therapy include angioplasty (with or without stents) for stenosis [14], stents for dissection, coils or stents for aneurysms and in some cases surgical procedure. Nature and position of vascular lesions, incidence and severity of symptoms before the vascular episodes, the occurrence and range of aneurysms and existence of other co-morbid conditions are all considered for deciding the course of treatment.

The efficacy of various treatment for FMD is not scientifically validated and natural history is also not available. Antiplatelet treatment is opted for ischemic stroke patients despite the lack of scientific evidence to demonstrate its efficacy in managing symptomatic FMD patients. Surgical interventions can be opted in symptomatic FMD patients with low perioperative risk. Surgery is relatively risk free procedure as most of the techniques are well known and outcome of such interventions was found to have an impressive long-term anatomical result.

The most recent studies point out the efficacy of percutaneous angioplasty in having fewer complications compared to the other techniques. Thus percutaneous angioplasty is the treatment offered for patients suffering recurring manifestation of FMD due to haemodynamic instability. However the long term effect of such treatment is yet to be studied [15].

Prognosis

Prognosis data of FMD is not available owning to its symptomatic and benign nature. Progress of FMD was shown to have positive outcome with stroke free survival for longer periods in studies involving patients who were medically and surgically managed. A 4 year follow up study in 1981 by Collins et al on 18 patients who underwent surgical dilatation revealed that none of them had stroke under the study period [11]. The study included 5 patients presenting global symptoms  who underwent conservative therapy for about 42 months.

The detection of FMD in autopsy series is highly biased in saccular aneurysm rupture cases with high mortality rate. Out of the carotid artery dissection patients who had a recurrence in a 4 years study (5 of 103), 80% was found to have FMD [7].

Etiology

The precise reason or risk factors for developing of FMD is unknown despite several studies [4]. It is postulated that many underlying factor may contribute to the development of FMD. The major factors that has a detrimental role include [5]:

  • Hormonal influence: FMD is reported most commonly in women. The female hormones might play an important role in FMD development.
  • Genetics: Patients (7-11%) with clinically diagnosed FMD has a familial history of FMD. Genetic abnormalities of vascular system may also lead to FMD.
  • Internal mechanical stress : The arterial walls that endure trauma and the mechanical forces may lead to FMD.
  • Poor oxygen supply: Presence of fibrous lesions on the arterial walls lead to obstruction of oxygen rich blood supply. This pathological condition may result in FMD.

Epidemiology

Series of studies based on the autopsy and radiologic reports formerly estimated the incidence of craniocervical FMD as 1%. However this data has been recently corrected to 0.02% based on a larger series of study [6]. FMD is often asymptomatic and is diagnosed accidentally. Mortality and morbidity data of FMS thus largely remains unavailable. Cranial involvements sometimes may lead to poor prognosis owning to multiple factors like incidence of strokes and dissection and also due to coexistence of saccular aneurysms.

de Bray et al reviewed and followed up 103 carotid artery dissection patients for about 4 years in order to determine the risk of recurrence. It was observed that 5 patients suffered a recurrent episode of carotid artery dissection and 4 out of the 5 patients had FMD. Based on this data it can be assumed that 80% of carotid artery dissection recurrence is associated with FMD [7].

Sex distribution
Age distribution

Pathophysiology

The pathophysiology of FMD largely remains vague. Higher prevalence of FMD in female implies a role of estrogen. The preponderance of right renal artery FMD suggest involvement of mechanical component owning to the increased mobility of right kidney. Ischemia from vasa vasorum compression may possibly lead to FMD. Vasa vasorum are minute blood vessels that supply blood to adventitia and the external two-third of the media of arteries larger than 1 mm. Carotid and renal arteries have relatively few of them leading to an heighten possibility of FMD [8]. Smoking is also considered as a predisposing factor. About 6 to 10% of inherited FMD is through autosomal dominant transmission with reduced penetrance and variable expressivity. The specific gene responsible for this has not been identified so far [9]. In a series of angiogram study conducted on 106 patients over 9 years revealed that FMD either progress or stabilize over the course of time but none was found on have a regression [10].

Prevention

FMD is generally not considered as preventable disease. Cigarette smoking is observed as a risk factor in developing FMD so avoiding smoking may help in minimizing the chance of development of FMD.

Summary

Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease resulting in arterial stenosis, occlusion, dissection or aneurysm [1] [2]. The etiology and occurrence of FMD in general population remain largely unknown despite many studies [3]. FMD is known to affect almost every arterial bed but renal, vertibral and extracranial carotid FMD account for approximately 65% of the total cases [4]. The clinical presentation of FMD depends upon the affected blood vessels. Renal artery FMD is presented as hypertension and vertebral or carotid artery FMD manifest itself in the form of dizziness, pulsatile tinnitus, stroke or transient ischemic attack (TIA).

An average delay of 4 to 9 years is generally observed from the time of initial clinical manifestation to diagnosis of FMD [4]. The main reasons for the delay is attributed to a number of facts like:

  • FMD is often considered as a rare disease and therefore is not a primary suspect in many clinical cases 
  • Poor understanding of FMD by many physicians
  • Non specific nature of presentation leading to incorrect diagnostic pathway

Failure in early FMD diagnosis negatively influence the patient resulting in poor prognosis and health conditions. For e.g. poorly managed hypertension often leads to stroke, TIA, dissection or aneurysm rupture. Most frequently FMD is diagnosed accidentally through imaging tests which is performed for other clinical reasons or through the incidental discovery of bruit  in the abdomen or neck of asymptomatic patient with no atherosclerosis risk factors. 

Patient Information

FMD is a nonatherosclerotic and noninflammatory disease affecting the musculature of arterial vessels. It leads to abnormal narrowing (stenoses) for arteries. FMD mainly effects renal and cervicocerebral arteries resulting in renal hypertension and cerebral ischemia (restriction in blood supply) respectively. The cause of FMD is not known, however many factors that are believed to play a role: 

  • Genetics: Familial history of FMD is reported in some cases.
  • Hormones: Higher incidence of FMD in women indicates a hormonal link. However there is no evidence of FMD being linked to the pregnancies or to the administration of birrth control pills.
  • Abnormality of arteries: Insufficient oxygen supply to the arteries that provide blood to the wall of blood vessel may lead to FMD. This can happen when the arteries are not positioned correctly. Certain medications or tobacco abuse can also lead to arterial abnormality. Abnormal arterial walls allow clustering of cells leading to obstruction and reduction in blood supply to the affected area.

Symptoms

FMD is generally asymptomatic and are typically detected incidentally. FMD can become symptomatic at any age and the symptoms presented largely depend upon the location of affected artery. FMD of renal artery present itself as hypertension. Renal FMD may result in renal artery dissection followed by renal infarction and in case of renal artery aneurysm rupture internal hemorrhage may occur. Headaches, pulsatile tinnitus, Horner's syndrome, arterial bruit, TIA or stroke are the symptoms suggestive of cervico-cerebral FMD (stenosis or dissection). Intracerebral aneurysms may sometime present as subarachnoid hemorrhage. Acute coronary syndrome, intestinal ischemia and leg pain are the symptoms observed in case of coronary, visceral and lower limb FMD respectively.

Diagnosis

  • FMD are generally detected in the form of beaded arteries during X-ray or other image studies conducted for diagnosis of another ailments.
  • Detection of bruit (swooshing noise) indicating abnormal blood flow may be due to FMD.
  • Detection of FMD in one region warrants more imaging tests to check out the presence of FMD in other parts. For e.g. if a patent is diagnosed with carotid FMD and hypertension, tests are done to detect FMD in renal arteries.
  • Confirmation of FMD and the extent of FMD lesions are studied using non invasive imaging tests like MRA, doppler ultrasound or CTA.
  • When diagnosis of FMD is inconclusive, the doctor may opt for dye angiogram - the gold standard for detecting FMD.
  • In confirmed FMD cases, presence of aneurysm in brain or aortic branches should to checked and must be given extra treatment.

Treatment

Antihypertensive medical treatment is opted for managing hypertension with renal artery FMD. In patients suffering from resistance or intolerance to medicines, percutaneous angioplasty or surgery is opted. Revascularization helps in preventing ischemic events in symptomatic cervico-cerebral FMD patients. Endovascular coiling or surgical clipping is performed for managing intra-cranial aneurysm.

References

Article

  1. Olin JW, Sealove BA. Diagnosis, management, and future developments of fibromuscular dysplasia. J Vasc Surg. 2011; 53:826–836.e1.
  2. Persu A, Touze E, Mousseaux E, et al. Diagnosis and management of fibromuscular dysplasia: an expert consensus. Eur J Clin Invest. 2012; 42:338–347. 
  3. Slovut DP, Olin JW. Fibromuscular dysplasia. N Engl J Med. 2004; 350:1862–1871.
  4. Olin JW, Froehlich J, Gu X, Bacharach JM, et al. The United States registry for fibromuscular dysplasia: results in the first 447 patients. Circulation. 2012; 125:3182–3190.
  5. Luscher TF, Lie JT, Stanson AW et al. Arterial fibromuscular dysplasia. Mayo Clin Proc 1987; 62: 931–952.
  6. Heffelfinger MJ, Holley KE, Havrison EG. Arterial fibromuscular dysplasia studied at autopsy [abstract]. Am J Clin Pathol. 1970; 54:274.
  7. de Bray JM, Marc G, Pautot V, et al. Fibromuscular dysplasia may herald symptomatic recurrence of cervical artery dissection. Cerebrovasc Dis. 2007; 23(5-6):448-452. 
  8. Schievink WI, Bjornsson J. Fibromuscular dysplasia of the internal carotid artery: a clinicopathological study. Clin Neuropathol. 1996; 15(1):2–6.
  9. La Batide A, Perdu J, Ploin P. Dysplasie fibromusculaire artérielle. Press Med. 2007; 36:1016–1023
  10. Mettinger KL. Fibromuscular dysplasia and the brain. II. Current concept of the disease. Stroke. 1982; 13(1):53–58.
  11. Collins GJ Jr, Rich NM, Clagett GP, et al. Fibromuscular dysplasia of the internal carotid arteries. Clinical experience and follow-up. Ann Surg. 1981; 194(1):89-96.
  12. Arunodaya GR, Vani S, Shankar SK, et al. Fibromuscular dysplasia with dissection of basilar artery presenting as "locked-in-syndrome". Neurology. 1997; 48(6):1605-1608.
  13. Kim SD, Park JO, Kim SH, et al. Spontaneous thoracic spinal subdural hematoma associated with fibromuscular dysplasia. J Neurosurg Spine. 2008; 8(5):478-481.
  14. O'Connor S, Olin JW, Gornik HL. Top 8 lessons learned from the US Registry for FMD. Endovasc Today. 2014; 2:31-27.
  15. Touze E, Oppenheim C, Trystram D, et al.  Fibromuscular dysplasia of cervical and intracranial arteries. Int J Stroke. 2010; 5(4):296–305.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2018-06-21 23:10