eMedicine Specialties > Neurology > Neuro-vascular Diseases
Fibromuscular Dysplasia: Treatment & Medication
Updated: Aug 30, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Partly because of the unknown etiology of FMD, no curative therapy exists. Fortunately, FMD is often benign when asymptomatic, and medical treatment is not indicated. Patients presenting with hypertension should be evaluated by a nephrologist and possibly considered for vascular intervention.
When FMD manifests as a transient ischemic attack or as an ischemic stroke, then initial management depends on many factors. If the patient presents in the emergency department with symptoms of stroke within 3 hours of onset, then they may be considered for intravenous (IV) tissue plasminogen activator (tPA) treatment (see Acute Stroke Management). Intra-arterial mechanical embolectomy and intra-arterial pharmacologic fibrinolysis may be considered to extend the acute treatment window to 6 hours. If TPA treatment is employed, then anticoagulants and antiplatelet agents are avoided for at least the ensuing 24 hours.
The diagnosis of FMD should be considered in any young individual presenting with a stroke or subarachnoid hemorrhage. Fortunately, cerebral angiography is the investigation of choice to detect not only FMD but also arterial dissection, vasculitis, and aneurysms, which are other major etiologies of stroke in this population. Thus, cerebral angiography should be performed if another cause for the stroke is not clear. The treatment options are influenced by the findings on angiography.
If only FMD is identified on angiography, medical treatment usually incorporates antiplatelet agents, similar to the treatment of atherosclerotic disease. Often, daily aspirin is considered first-line therapy, and another antiplatelet agent is substituted or added if another ischemic event occurs (such as clopidogrel or combination acetylsalicylic acid and extended-release dipyridamole).
If arterial dissection with FMD is identified with cerebral angiography, then initial treatment primarily addresses the dissection (see Dissection Syndromes). Although evidence from randomized trials is lacking, anticoagulation is often used after cerebral hemorrhage has been ruled out. Anticoagulation is with heparin initially, then Coumadin is administered on an outpatient basis for 3-6 months. Some neurologists advocate reassessment of the arteries for dissection before discontinuation of anticoagulation and initiation of an antiplatelet agent for life. Often, if the dissection could be observed with MRA or CTA, these modalities are used in follow-up because of its less invasive nature.
If the presentation is that of subarachnoid hemorrhage, then acute treatment is primarily focused on preventing rebleeding, and preventing arterial vasospasm and further ischemic cerebral injury. Aneurysms may be closed by endovascular coiling or surgical clipping. Nimodipine, a calcium channel blocker, is generally used to reduce vasospasm-mediated brain injury. See Cerebral Aneurysms for a more in-depth discussion of aneurysm management.
After the aneurysms have been dealt with, either surgically or through an endovascular approach, then unless further history is consistent with thromboembolic phenomena, management may be conservative. Antiplatelets are unnecessary if the FMD lesions themselves are asymptomatic and not causing emboli.
Surgical Care
Surgical vascular reconstruction of renal FMD has met with good success.29 However, because the end organ of cervicocranial FMD is the brain, more serious risks are involved. Thus, the role of surgery in carotid and vertebrobasilar FMD is not well understood.
Although medical management of stroke prophylaxis in FMD is quite similar to the management of atherosclerotic disease, the lesions in FMD are not amenable to endarterectomy. Thus, surgical management is used as a last resort in cases where stenosis is critical and global cerebral hypoperfusion is an issue or for ischemic events refractory to medical management. No trials exist comparing medical and surgical management of cerebrovascular FMD. However, many authors have published series of operative graduated dilatation of FMD stenosis and report good results.30,31,32 A few cases with vascular graft placements and surgical bypass of FMD lesions have been reported.
Aneurysms that may coexist with FMD should be managed in a similar manner to non-FMD–associated ones.
Because of the emergence of endoluminal angioplasty and stenting for cerebrovascular disease, interventional radiologic management of FMD lesions may be suitable for some patients, especially those who are not good surgical candidates. Again, no studies have assessed this management option as compared to more established medical or surgical treatment, but it may be deemed an appropriate option in some instances. One case report describes a good outcome after 9 months of follow-up in a patient with bilateral carotid stents placed for bilateral medically-refractory symptomatic lesions.33
Consultations
A stroke presentation, whether acute or not, is usually managed by a neurologist. If associated aneurysms or subarachnoid hemorrhages are detected, then a neurosurgeon and interventional radiologist should be consulted. If a history of chest pain is noted, this may signify FMD in the coronary arteries, and a cardiologist should be consulted. If blood pressure is elevated, then the renovasculature should be assessed and a nephrologist consulted if necessary. Symptoms of an ischemic gut should be managed by a general surgeon, and limb claudication should be assessed by a vascular surgeon.
Diet
No specific dietary modifications are indicated in FMD. If a stroke has occurred, then a swallowing assessment may be required and the diet modified accordingly.
Activity
Activity restrictions should be individualized depending on the clinical details and possible neurologic deficits. Neck trauma, including chiropractic manipulation, should be avoided if craniocervical FMD is established because of the possibility of dissection. If cerebral aneurysms exist, strenuous activity that would increase blood pressure should be avoided.
Medication
As discussed above, acute treatment of any ischemic stroke may involve tPA, regardless of the presence or absence of FMD.
Secondary prevention of stroke generally involves the use of antiplatelet agents, and failure of a first agent results in either the switch to another agent or the addition of a second antiplatelet agent. Selection of a particular antiplatelet agent is variable, depending on physician preference. The complication of arterial dissection is generally treated with anticoagulation, first intravenously then orally. Finally, subarachnoid hemorrhage due to aneurysm rupture precludes anticoagulation and indicates a need for antivasospastic medications.
Fibrinolytic agents
tPA exerts an effect on fibrinolytic system to convert plasminogen to plasmin. They are used for dissolving blood clots and have a role in the acute management of ischemic strokes.
Alteplase (Activase)
Used in management of acute ischemic stroke, acute MI, and PE. Safety and efficacy with concomitant heparin or aspirin during first 24 h after symptom onset not investigated.
Adult
0.9 mg/kg IV over 60 min; 10% of total dose administered as initial IV bolus over 1 min; not to exceed 90 mg
Pediatric
Not established
Anticoagulants and antiplatelet agents may increase risk of bleeding; heparin with and after infusions to reduce risk of rethrombosis may increase risk of bleeding complications
Documented hypersensitivity, active internal bleeding, prior stroke or stroke within 2 mo, intracranial or intraspinal surgery or trauma, ICH (rule out with CT when used for stroke treatment), suspected subarachnoid hemorrhage, intracranial neoplasm, arteriovenous malformation or aneurysm, bleeding diathesis, severe uncontrolled hypertension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor for bleeding, especially at arterial puncture sites; frequently control and monitor BP during and after administration (in acute ischemic stroke); do not use >0.9 mg/kg to manage acute ischemic stroke; doses >0.9 mg/kg may cause ICH
Antiplatelet agents
These agents are used for secondary stroke prophylaxis after previous stroke or transient ischemic attack.
Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)
Treats mild to moderate pain and headache. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2. Generally considered first-line therapy in the secondary prophylaxis of cerebrovascular disease.
Adult
80 mg PO qd is generally sufficient; some suggest 325 mg qd
Pediatric
Not established
Antacids and urinary alkalinizers may decrease effects; corticosteroids decrease serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses > 2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; use in children <16 y with flu (association with Reye syndrome)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, those with history of blood coagulation defects, and those taking anticoagulants
Clopidogrel (Plavix)
Selectively inhibits ADP binding to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, inhibiting platelet aggregation.
May have positive influence on several hemorrhagic parameters and may exert protection against atherosclerosis (inhibition of platelet function and changes in hemorrhagic profile).
Adult
75 mg PO qd
Pediatric
Not established
Coadministration with naproxen associated with increased occult GI blood loss; clopidogrel prolongs bleeding time; safety with warfarin not established
Documented hypersensitivity; active pathologic bleeding, such as peptic ulcer or intracranial hemorrhage
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients at increased risk of bleeding from trauma, surgery, or pathologic conditions; caution in patients with lesions with propensity to bleed (eg, ulcers)
Ticlopidine (Ticlid)
Second-line antiplatelet therapy for patients who cannot tolerate acetylsalicylic acid therapy or for whom such therapy is unsuccessful. Rarely used because of serious adverse effects and replacement by newer agents.
Adult
250 mg PO bid
Pediatric
Not established
Corticosteroids and antacids may decrease effects; toxicity increases with concurrent theophylline, cimetidine, aspirin, and NSAIDS
Documented hypersensitivity; neutropenia or thrombocytopenia; liver damage; active bleeding disorders
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue if absolute neutrophil count <1200/mm3 or if platelet count <80,000/mm3
Aspirin 25 mg/Dipyridamole 200 mg (Aggrenox)
Drug combination with antithrombotic action. Aspirin inhibits prostaglandin synthesis, preventing formation of platelet-aggregating thromboxane A2. May be used in low dose to inhibit platelet aggregation and improve complications of venous stasis and thrombosis. Dipyridamole is a platelet adhesion inhibitor that possibly inhibits RBC uptake of adenosine, itself an inhibitor of platelet reactivity. May also inhibit phosphodiesterase activity, leading to increased cyclic-3', 5'-adenosine monophosphate levels in platelets and formation of the potent platelet activator thromboxane A2.
Adult
1 tab PO bid
Pediatric
Not established
Theophylline may decrease hypotensive effects of dipyridamole; antiplatelet activity of dipyridamole may increase heparin toxicity; antacids and urinary alkalinizers may decrease aspirin effects; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses > 2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; use in children <16 y with flu (association with Reye syndrome)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Aspirin may cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, those with history of blood coagulation defects, or those taking anticoagulants; caution in hypotension; dipyridamole has peripheral vasodilating effects
Anticoagulants
The use of anticoagulation in the acute management of stroke has been under hot debate for many years. However, many neurologists advocate the use of heparin acutely in stroke in the setting of an arterial dissection. Heparin is used acutely in this case, followed by several months of warfarin.
Heparin
Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.
Most centers have protocols to titrate heparin rate to achieve specific anticoagulation levels on blood work.
Adult
Starting does: <60 U/kg (maximum, 4000 U) IV bolus followed by a maintenance infusion of <12 U/kg/h (maximum, 1000 U/h) then adjust to PTT
Pediatric
Not established
Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, acetylsalicylic acid, dextran, dipyridamole, and hydroxychloroquine may increase heparin toxicity
Documented hypersensitivity; subacute bacterial endocarditis; active bleeding; history of heparin-induced thrombocytopenia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
In neonates, preservative-free heparin recommended to avoid possible toxicity (gasping syndrome) by benzyl alcohol (preservative); caution in severe hypotension and shock; monitor for bleeding in peptic ulcer disease, menstruation, increased capillary permeability, and IM injections
Warfarin (Coumadin)
Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders.
Adult
3-15 mg/d PO qd for 2-5 d; adjust dose to desired INR (for dissection, INR = 2-3)
Pediatric
Administer weight-based dose of 0.05-0.34 mg/kg/d PO; adjust dose to desired INR
Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, PO contraceptives, and sucralfate; medications that may increase anticoagulant effects of warfarin include PO antibiotics, capecitabine, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac
Documented hypersensitivity; severe liver or kidney disease; open wounds or GI ulcers
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Use caution and increase monitoring if switching brands after achieving therapeutic response; caution in active tuberculosis or diabetes mellitus; patients with protein C or S deficiency are at risk for skin necrosis
Calcium channel blockers
These agents are used in cases of subarachnoid hemorrhage.
Nimodipine (Nimotop)
To improve neurologic impairments resulting from vasospasm after subarachnoid hemorrhage caused by a ruptured congenital intracranial aneurysm in patients who are in good neurologic condition postictus.
Studies show benefit on the severity of neurologic deficits caused by cerebral vasospasm after subarachnoid hemorrhage, but no evidence indicates that the drug either prevents or relieves spasm of the cerebral arteries. Actual mechanism of action unknown, and a neuroprotective effect is suggested.
Therapy should start within 96 h of the subarachnoid hemorrhage. If capsule cannot be swallowed because patient is undergoing surgery or unconscious, a hole can be made at both ends of the capsule with an 18-gauge needle and the contents extracted into a syringe and emptied into the patient's in situ nasogastric tube and flush with 30-mL isotonic saline.
Adult
60 mg PO q4h for 21 consecutive d
Pediatric
Not established
Although advantageous in some patients, coadministration with beta-blockers may increase adverse effects because of depressant effects on myocardial contractility or AV conduction; when administered with fentanyl, severe hypotension or increased fluid volume requirements may occur in patients receiving calcium blockers; cimetidine may increase blood levels of nimodipine
Documented hypersensitivity; <90 mm Hg systolic pressure; sick sinus syndrome; second- or third-degree AV block except when using a pacemaker
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Rare cases of elevated LDH, alkaline phosphatase, and ALT levels may occur
More on Fibromuscular Dysplasia |
| Overview: Fibromuscular Dysplasia |
| Differential Diagnoses & Workup: Fibromuscular Dysplasia |
 Treatment & Medication: Fibromuscular Dysplasia |
| Follow-up: Fibromuscular Dysplasia |
| Multimedia: Fibromuscular Dysplasia |
| References |
| « Previous Page | Next Page » |
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Further Reading
Keywords
FMD, fibromuscular hyperplasia, medial hyperplasia, arterial fibrodysplasia, angiopathy, renal artery disease, stroke
