Fibromuscular Dysplasia FMD

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Fibromuscular Dysplasia (FMD)
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Table of Contents

• Fibromuscular Dysplasia Overview
• Histology
• Components of Vascular System
• Pathology
• Etiology
• Clinical Presentation
• Associated Diseases
• FMD Discussion by Arterial Involvement
• Renal Arterial Involvement
• Mechanisms of Hypertension
• Natural History
• Diagnosis
• Treatment

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Table of Contents (Continued)

• FMD Discussion by Arterial Involvement (cont.)
• Carotid Arterial Involvement
• Natural History
• Diagnosis
• Treatment
• Associated Conditions
• Non-Renal Abdominal Viscera Presentation and
  Treatment
• Peripheral Artery Disease
• Case Studies

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Fibromuscular Dysplasia (FMD)

• Nonatherosclerotic, noninflammatory disease
• More common in women and younger individuals
• The incidence of FMD in children is unknown.
• Described in almost every vascular bed1
• Renal arteries (60-75)
• Cervicocranial arteries (25-30)
• Non-renal visceral arteries (9)
• Arteries in the extremities (5)
• Others including pulmonary and coronary arteries
• Multiple vascular beds in 28 of patients2

1Gray BH et al In Peripheral Vascular Diseases
1996, 2Lüscher TF et al Nephron 1986
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FMD - Histology of Arteries

• Lumen
• Endothelium (basal lamina)
• Intima
• Internal elastic lamina
• Media
• External elastic lamina
• Adventitia

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Components of the Vascular System
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Elastic Laminae in a Large Artery
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FMD - Pathologic Classification

• Intimal fibroplasia (less than 10)
• Medial dysplasia
• Medial fibroplasia (80)
• Perimedial fibroplasia (10-15)
• Medial hyperplasia (1-2)
• Adventitial (periarterial) fibroplasia

Harrison EG Jr and McCormack LJ Mayo Clinic Proc
1971
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FMD Pathology - Intimal Fibroplasia

• Children and young adults
• Circumferential deposition of collagen in the
  intima, often projecting into lumina
• Internal elastic lamina may be duplicated or
  disrupted but can be identified
• Long, irregular (tubular) or focal, smooth
  (concentric band) stenoses1

1Stanley JC et al Arch Surg 1975
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FMD Pathology - Intimal Fibroplasia
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FMD Pathology - Medial Fibroplasia

• 25-50 year old women
• Thickened media alternating with thinned media ?
  aneurysmal dilatation
• String of beads
• Thickened media is replaced by collagen
• Internal elastic lamina may be thinned or
  fragmented
• May lead to macroaneurysm formation1
• Frequently affects the renal arteries bilaterally

1Stanley JC Arch Surg 1975
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FMD Pathology- Perimedial Fibroplasia

• 15-30 year old women
• Collagen deposition in the outer half of the
  media replacing the external elastic lamina
  intact adventitial connective tissue
• String of beads
• Can result in severe stenosis
• Often associated with collateral circulation
• Preferentially affects the renal artery (mid
  portion)

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FMD Pathology - Adventitial (periarterial)
Fibroplasia

• Adventitial (periarterial) fibroplasia
• Very rare
• Collagen replaces the fibrous adventitia
• May extend beyond artery

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FMD - Etiology

• Genetic
• Autosomal dominant with variable penetrance in
  60 of cases based on clinical symptoms1
• 11 prevalence angiographically2
• Hormonal
• No difference in gravidity or parity rates,
  effect on disease progression3
• Oral contraceptive pill use?4,5,

1Rushton AR Arch Intern Med 1980, 2Pannier-Moreau
I et al J of Hypertens 1997, 3Stanley JC et al
Arch Surg 1975, 4Sang CH et al
Hypertension 1989, 5Hardy-Godon S et al J of
Neuroradiol 1979
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FMD - Etiology

• Mechanical
• Ptosis of the right kidney1
• Repetitive trauma such as hyperextension and
  rotation of the neck1
• Mural ischemia
• Occlusion of the vasa vasorum2
• Vasospasm (ergotamines, methysergide)3
• Tobacco use4

1Lüscher TF et al Mayo Clin Proc 1987, 2Sottiurai
V et al J of Surg Res 1978,
3Fievez ML Med Hypotheses
1984, 4Sang CN et al Hypertension1989
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FMD - Clinical Presentation

• Asymptomatic
• Nonspecific symptoms
• Headaches, altered mentation, tinnitus, vertigo,
  carotidynia
• Neurologic symptoms
• Transient ischemic attacks, cerebral infarctions,
  subarachnoid hemorrhages, syncope, Horners
  syndrome, cranial nerve palsies

Mettinger KL and Ericson K Stroke 1982, Houser OW
et al Radiology 1971
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FMD - Associated Diseases

• Turners syndrome
• Alports syndrome
• Neurofibromatosis
• Coarctation of the aorta
• Moyamoya disease

• Cystic medial necrosis
• Hypertrophic cardiomyopathy
• Heterozygous a1- antitrypsin deficiency
• Pheochromocytoma

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Arterial Involvement
Slovut DP et al N Engl J Med 20043501862
19
Renal Arteries

• Leadbetter and Burkland (1938) reported the first
  case of FMD1
• 40 of all patients with renovascular disease
  have FMD2
• Symptomatic patients present with hypertension
• Onset of hypertension before age 30
• Epigastric bruit (systolic/diastolic)3
• Less frequently develop ischemic renal atrophy
  and chronic renal failure

1Leadbetter WF and Burkland CE J Urol 1938, 2
Olin JW and Novick AC In Peripheral Vascular
Diseases 1996, 3Eipper DF et al Am J of Cardiol
1976
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Renal Arteries
Panel A shows string of beads. Panel B shows
gadolinium-enhanced MRA revealing
bilateral medial fibroplasia of the renal
arteries.
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Renal Arteries - Mechanism of Hypertension
Ischemia
Renin
Angiotensinogen ? Angiotensin I ? Angiotensin II
Direct Vasoconstriction Aldosterone Secretion
Salt Water Retention
22
Upper Percentiles ofBlood Pressure forGirls
The Fourth Report on the Diagnosis, Evaluation,
and Treatment of High Blood Pressure in Children
and Adolescents Pediatrics 114(2) Part 3 of 3
August 2004.
23
Upper Percentiles ofBlood Pressure forBoys
The Fourth Report on the Diagnosis, Evaluation,
and Treatment of High Blood Pressure in Children
and Adolescents Pediatrics 114(2) Part 3 of 3
August 2004.
24
Renal Arteries - Natural History

• Angiographically-proven progression
• Goncharenko (1981) 42/42 patients
• Follow-up 1 136 months
• 75 bilateral, 29 medial FMD, 62 change in
  kidney size ? 0.5 cm
• Schreiber (1984) 66 patients with medial FMD
• Follow-up 45 months angio, 104 months clinical
• 33 progression 9 increase in creatinine, 27
  atrophy of ipsilateral kidney (? 1.5 cm)

Goncharenko V et al Radiology 1981, Schreiber MJ
et al Urol Clin of North Am 1984
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Renal Arteries - Natural History

• Clinically-proven progression
• Cragg (1989) 71 potential kidney donors (f/up
  49)
• 26.6 developed hypertension at 7.5 years (30 w/o
  nephrectomy)
• 26.3 developed hypertension at 4.4 years (19
  with nephrectomy)
• 6.1 age and sex-matched controls developed
  hypertension at 7.1 years
• Clinical progression may reflect the development
  of concomitant development of essential
  hypertension or atherosclerosis

Cragg AH et al Radiology 1989
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Renal Arteries - Diagnosis

• Captopril renography (functional)
• Spiral CT angiography1
• Transverse sections and maximum-intensity
  projections
• MR angiography2
• Duplex Ultrasonography
• Color power angio
• Angiography

1Beregi J-P et al AJR 1999, 2Leung DA et al
Hypertension 1999
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Renal Arteries Diagnosis - Duplex Ultrasonography
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Renal Arteries - Treatment

• Stop smoking
• Antiplatelet therapy
• Medical therapy following JNC-VI guidelines1 and
  The Fourth Task Force Report2
• Unilateral disease?angiotensin-converting enzyme
  inhibitor, angiotensin II antagonist
• Bilateral disease?diuretic/calcium channel blocker

1JNC-VI Guidelines Arch Intern Med 1997
2The Fourth Report Pediatrics 114(2) Part 3 of 3
August 2004
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Renal Arteries - Indications for Intervention

• Blood pressure cannot be controlled despite three
  antihypertensive medications at maximal doses
• The individual is intolerant to the medications
• Compliance is an issue
• An alternative to lifelong dependency on a
  medication in a relatively young individual

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Renal Arteries - Endovascular TherapyBP
Ramsey LE and Waller PC BMJ 1990, Tegtmeyer CJ et
al Circulation 1991,
Bonelli FS et al Mayo Clin Proc 1995,
Kløw N-E et al Acta Radiol 1998
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Renal Arteries - Endovascular Therapy CRI
Tegtmeyer CJ et al Circulation 1991
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Renal Arteries - Endovascular Therapy Branch
Lesions

• Segmental renal arteries are affected in 30-56
  of patients with FMD
• Cluzel (1994) 20 patients with 25 arteries
• Technical success rate 84
• 91 patency rate at 6 months
• Hypertension cure
• Post-PTRA 70, 6-month 76, long-term 68
• Hypertension improved
• Post-PTRA 25, 6-month 24, long-term 16

Cluzel P et al Radiology 1994
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Renal Arteries Intervention Complications

• Puncture site
• AVF, pseudoaneurysm, bleeding/hematoma, femoral
  nerve injury, infection
• Catheter-related
• Dissection, perforation/rupture, AED, balloon
  rupture, thrombosis, renal artery spasm
• Contrast Media
• ARF, anaphylaxis
• Medical

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Renal Arteries Predictors of Cure of
Hypertension in FMD

• Younger patients with milder hypertension of a
  shorter duration were most likely to be cured.
• Some patients with an extremely low chance of
  cure might be managed with a trial of medical
  therapy
• FMD is unlikely to progress to renal failure

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Renal Arteries - Surgery

• Indications
• Lack of endovascular expertise, recurrent
  disease, inaccessible branch lesions
• Approaches
• Aortorenal bypass, extracorporeal
  revascularization autotransplantation, spleno-
  or hepato-renal
• Blood pressure
• 36-63 cure, 30-50 improvement
• Outcomes
• Low morbidity and mortality

Hansen KJ et al J Vasc Surg 1992, Novick AC et al
JAMA 1987, Reiher L et al Eur J Endovasc Surg 2000
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Renal Arteries - Surgery

• 45 children with renovascular FMD, 17 with aortic
  involvement
• Average age at diagnosis was 9 years
• Three with renal failure
• Twenty-three of the 45 had bilateral vessel
  involvement
• A variety of surgical approaches were used
  depending on the pathology encountered
• Thirty-eight patients underwent
  revascularization, seven underwent primary
  nephrectomy, five underwent primary partial
  nephrectomy, and 12 had aortoaortic bypass
  performed
• Seventy percent were cured, 26 improved and 4
  did not respond to treatment with up to 16 years
  of follow-up
• There was no mortality.

O'Neill JA Jr.Long-term outcome with surgical
treatment of renovascular hypertension. Pediatr
Surg 199833(1)106-11
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Carotid Arteries

• Palubinskas and Ripley (1964) described a case of
  FMD involving the extracranial internal carotid
  artery1
• Carotid arteries (95) frequently bilaterally2
• Vertebral involvement is rare and usually
  associated with carotid involvement3
• Predominately affects extracranial segments

1Palubinskas AJ and Ripley HR Radiology 1964,
2Healton EB In StrokePathophysiology, Diagnosis,
and Management 1986, 3Osborn AG and Anderson RE
Stroke 1977
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Carotid Arteries
Panel C, a 16 row multidetector of the ICA
Panel D, duplex ultrasonography of the
ICA.
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Carotid Arteries

• See Examples of FMD

Panel A severe concentric stenosis in the ICA.
Panel B ICA after percutaneous angioplasty.
Panel C shows sever redundancy a kink in the
distal ICA.
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Carotid Arteries - Natural History

• Look at clinical outcome, not angiographic
  progression
• Corrin (1981) 79 patients, 3 strokes (3.8)
• 13 TIA/CVA, 10 SAH, TX 4 OR, 11 med
• Wells (1982) 17 patients, 2 strokes (13)
• 9 TIA, TX 1 OR, 3 med
• Stewart (1986) 45 patients, 0 strokes (0) in the
  35 who did not have an operation
• 10 OR lt3mos, 23/35 TIA/CVA only 1 symptomatic

Corrin LS et al Arch Neurol 1981, Wells RP and
Smith RR
Neurosurgery 1982, Stewart MT
et al J Vasc Surg 1986
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Carotid Arteries - Diagnosis

• Angiography remains the gold standard
• String of beads, smooth tubular stenoses,
  diverticula, well-defined webs or septations1
• FMD has been associated with carotid kinks2
• Carotid duplex ultrasonography3
• Magnetic resonance angiography4

1Osborn AG and Anderson RE Stroke 1977,
2Schneider PA and Rutherford RB In Vascular
Surgery 2000, 3Boespflug OJM
Neuroradiology 1985, 4Heiserman JE et al AJNR 1992
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Carotid Arteries - Treatment

• Stop smoking
• Antiplatelet therapy
• Intervention
• Surgery including a resection with end-to-side
  anastomosis (or interposition graft),
  endarterectomy, carotid-middle cerebral artery
  bypass
• Graduated intraluminal dilatation
• Percutaneous transluminal angioplasty

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Carotid Arteries - Treatment
Effeney DJ et al Arch Surg 1980, Moreau P et al
J Cardiovasc Surg 1993, Schneider PA
et al In Vascular SurgeryPrinciples
and Practice 1994, Chiche L et al Ann Vasc Surg
1997
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Carotid Arteries - Associated Conditions

• Intracranial berry aneurysms
• Incidence 21 to 511
• Multiple, found predominately in the internal
  carotid and middle cerebral arteries2
• Obtain a MRA for screening
• Dissections3
• Arteriovenous fistulas4

1Healton EB In StrokePathophysiology, Diagnosis,
and Management 1986, 2Mettinger KL Stroke 1982,
3Müller BT et al J Vasc Surg 2000, 4Hieshima GB
et al Neurosurgery 1986
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Non-Renal Abdominal Viscera

• Celiac, superior mesenteric, inferior mesenteric,
  hepatic, and splenic arteries
• More typically appear as long tubular stenoses1
• Component of a systemic process mimicking
  vasculitis (intimal FMD)

1Lüscher TF et al Mayo Clin Proc 1987
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Non-Renal Abdominal Viscera Presentation
Treatment

• Asymptomatic
• Mesenteric ischemia1
• postprandial pain, weight loss, epigastric bruit
• Abdominal pain due to ruptured aneurysm2
• Bowel infarction is rare3
• Treatment with percutaneous transluminal
  angioplasty or surgical revascularization

1Yamaguchi R et al Am J Gastro 1996, 2Jones HJ et
al J Rheumatol 1998,
3Hamed RMA and Ghandour K J Pediatr Surg 1997
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Peripheral Arterial Disease

• Lower extremities
• External iliac, femoral popliteal, tibial,
  peroneal
• Digital ischemia, intermittent claudication,
  acute limb ischemia1
• Upper extremities
• Subclavian, axillary, brachial, radial, ulnar
• Arm claudication, paresthesias, subclavian steal
  syndrome, weakness, ischemic digits (hypothenar
  hammer syndrome)

1Sauer L et al J Vasc Surg 1990
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Summary

• FMD can occur in almost any arterial bed
• Angiography remains the diagnostic test of choice
  but other, less invasive techniques may be useful
• All patients must stop smoking and be treated
  with an antiplatelet agent
• Intervention should be reserved for symptomatic
  patients

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FMD Case Studies
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Case Study 1

• BP 170/105 mmHg on repeat measurements
• EKG/ECHO LV
• Metabolic panel normal

• MF a 14 year old male
• Routine physical examination found to have
  hypertension
• No symptoms or signs by history or on examination

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Case Study 1
DMSA shows no scarring with equal uptake by both
kidneys
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Case Study 1
Angiography
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Case Study 1
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Case Study 1

• Management
• Antihypertensives
• Right nephrectomy after failed repair to a large
  thin walled extra-parenchymal aneurysm
• Follow-up
• No further hypertension, off all medications. No
  indication of any further vessel involvement
  after 36 months follow up.

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Case Study 2

• GB 13 year male
• Presented with severe hypertension
• Found by routine school screening
• Poorly functional right kidney, small size ,
  severe right renal artery stenosis
• Normal left kidney and normal vessels
• Right nephrectomy off blood pressure
  medications

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Case Study 2

• GB now 15 years old
• Severe hypertension recurred
• Left kidney now with stenosis
• Repeated balloon dilatation
• Ongoing need for blood pressure medication

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Gerard Burns
Case Study 2
Left kidney with trident renal artery sub-branch
involvement
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Case Study 3

• LVH
• Non-functional right kidney with severe right
  renal artery narrowing
• Unilateral Nephrectomy
• No HTN after 3 years of follow up

• Patient JB
• Found to have HTN on routine Pediatricians visit
• Past history of trauma to the right flank and
  back related to baseball
• BP elevated to 160/100 mmHg

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For more information
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affected by Fibromuscular Dysplasia (FMD) by
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research towards new medical treatments and
diagnostic tools. P.O. Box 999, Hudson, OH
44236-0999 [phone] www.fmdsa.org
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